subject:(Antivirals)

Oregon State University

1. Lupfer, Christopher. Targeted development of antivirals against influenza A and respiratory syncytial virus.

Degree: PhD, Genetics, 2009, Oregon State University

URL: http://hdl.handle.net/1957/11948

► Influenza A and Respiratory Syncytial Virus (RSV) are both enveloped, negative strand RNA viruses which infect the respiratory mucosa of animals and humans. Despite decades… (more)

Subjects/Keywords: Antivirals; Influenza A virus

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APA (6^th Edition):

Lupfer, C. (2009). Targeted development of antivirals against influenza A and respiratory syncytial virus. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/11948

Chicago Manual of Style (16^th Edition):

Lupfer, Christopher. “Targeted development of antivirals against influenza A and respiratory syncytial virus.” 2009. Doctoral Dissertation, Oregon State University. Accessed April 17, 2021. http://hdl.handle.net/1957/11948.

MLA Handbook (7^th Edition):

Lupfer, Christopher. “Targeted development of antivirals against influenza A and respiratory syncytial virus.” 2009. Web. 17 Apr 2021.

Vancouver:

Lupfer C. Targeted development of antivirals against influenza A and respiratory syncytial virus. [Internet] [Doctoral dissertation]. Oregon State University; 2009. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/1957/11948.

Council of Science Editors:

Lupfer C. Targeted development of antivirals against influenza A and respiratory syncytial virus. [Doctoral Dissertation]. Oregon State University; 2009. Available from: http://hdl.handle.net/1957/11948

University of New South Wales

2. Enosi Tuipulotu, Daniel. Norovirus antiviral discovery: host-modulators and direct-acting antivirals.

Degree: Biotechnology & Biomolecular Sciences, 2018, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/62681 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:58917/SOURCE02?view=true

► Human norovirus is a leading cause of acute gastroenteritis (AGE) worldwide and is estimated to be responsible for over 200,000 deaths each year. Norovirus infections… (more)

▼ Human norovirus is a leading cause of acute gastroenteritis (AGE) worldwide and is estimated to be responsible for over 200,000 deaths each year. Norovirus infections are estimated to cost $60 billion in societal costs globally each year. Yet despite the substantial health and economic burden of norovirus, there is no vaccine or norovirus-specific antiviral approved for clinical use. Effective norovirus therapies are highly desired, particularly for the treatment of chronic norovirus infections, or for prophylaxis to limit outbreaks and protect high-risk groups, including the immunocompromised. Several direct-acting antivirals (DAAs) and host-targeted therapies have demonstrated inhibitory activity against noroviruses in vitro and in vivo, however none of these compounds have progressed through clinical trials. Therefore, this thesis aimed to discover new antivirals and expand the repertoire of compounds with the potential to be further developed for the treatment of norovirus infections. In the first study, RNA-sequencing was performed to provide insights into norovirus pathogenesis and to help identify new host targets that could be explored antiviral development. We found that norovirus infection dampens the transcriptional profile of several genes involved in MHC class I antigen presentation, likely for immune evasion. We also observed a significant reduction in TLR7 expression which could represent a mechanism to avoid recognition by the host. To explore this further, we screened several Toll-like receptor (TLR) agonists, currently in clinical trials for antiviral therapy, against norovirus and found that these compounds potently inhibit infection in vitro. Here we discovered a new target for norovirus antivirals. Lastly using in vitro antiviral assays against several caliciviruses, we discovered a new nucleoside analogue (NA), called NITD008, which represents the most potent NA described in the literature to date and a strong candidate for continued development. The new anti- norovirus compounds described in this thesis could be used as scaffolds for the generation of derivatives with improved drug properties or be used in combination with other compounds for improved efficacy. Overall, this thesis involved a multi-faceted approach to antiviral discovery which has increased the available compounds in the pre-clinical pipeline for norovirus therapy. Advisors/Committee Members: White, Peter, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, Edwards, Richard, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW.

Subjects/Keywords: Nucleoside analogue (NA); Norovirus; Antivirals

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APA (6^th Edition):

Enosi Tuipulotu, D. (2018). Norovirus antiviral discovery: host-modulators and direct-acting antivirals. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/62681 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:58917/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Enosi Tuipulotu, Daniel. “Norovirus antiviral discovery: host-modulators and direct-acting antivirals.” 2018. Doctoral Dissertation, University of New South Wales. Accessed April 17, 2021. http://handle.unsw.edu.au/1959.4/62681 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:58917/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Enosi Tuipulotu, Daniel. “Norovirus antiviral discovery: host-modulators and direct-acting antivirals.” 2018. Web. 17 Apr 2021.

Vancouver:

Enosi Tuipulotu D. Norovirus antiviral discovery: host-modulators and direct-acting antivirals. [Internet] [Doctoral dissertation]. University of New South Wales; 2018. [cited 2021 Apr 17]. Available from: http://handle.unsw.edu.au/1959.4/62681 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:58917/SOURCE02?view=true.

Council of Science Editors:

Enosi Tuipulotu D. Norovirus antiviral discovery: host-modulators and direct-acting antivirals. [Doctoral Dissertation]. University of New South Wales; 2018. Available from: http://handle.unsw.edu.au/1959.4/62681 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:58917/SOURCE02?view=true

University of New South Wales

3. Netzler, Natalie. Broad-spectrum antivirals targeting viruses from the caliciviridae and hepeviridae.

Degree: Biotechnology & Biomolecular Sciences, 2019, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/62685 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59105/SOURCE02?view=true

► Human pathogens from the Caliciviridae and Hepeviridae families impose a significant health and economic burden on our global society. Despite the substantial toll caused by… (more)

▼ Human pathogens from the Caliciviridae and Hepeviridae families impose a significant health and economic burden on our global society. Despite the substantial toll caused by viruses such as human norovirus, human sapovirus and hepatitis E virus (HEV), we currently have no specific antivirals available to combat these pathogens. The current therapies prescribed for chronic HEV infection are poorly tolerated and can result in treatment failure. Similarly, despite a significant body of research into identifying antivirals and vaccines for controlling human norovirus infections, none have achieved clinical approval. Safe and effective antivirals would be beneficial for the treatment of chronic norovirus and HEV infections and for prophylactic applications during outbreak and epidemic situations. The viral RNA-dependent RNA polymerase (RdRp) is a highly-conserved enzyme that is essential for viral replication and represents a prime antiviral target. Using in vitro polymerase activity assays and viral and replicon cell culture systems, this study describes the identification of broad-spectrum antivirals for further development against calicivirus pathogens and HEV. This study includes the first report of a class of hepatitis C virus (HCV) non-nucleoside inhibitors (NNIs) with cross-family antiviral activity, that demonstrated broad-spectrum inhibition of several calicivirus RdRps. A highly-conserved NNI binding pocket common to RdRps across the Caliciviridae was also identified, which represents a prime target for de novo antiviral design. A novel chemical scaffold is described with low micromolar activity against the human norovirus RdRp, that also demonstrated broad-spectrum activity against RdRps from across three Caliciviridae genera. Finally, an examination of antivirals previously developed against other viruses revealed three compounds with potent antiviral activity against replication of the HEV genotype 1 replicon, demonstrating that repurposing antivirals could provide an accelerated platform for HEV antiviral discovery. In conclusion, this thesis identified several broad-spectrum antivirals for further development against human pathogens such as HEV and norovirus, and a highly-conserved binding pocket for targeted norovirus antiviral design. Advisors/Committee Members: White, Peter Andrew, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, Eltahla, Auda, Medical Sciences, Faculty of Medicine, UNSW.

Subjects/Keywords: Norovirus; Antivirals; Broad-spectrum antivirals; Hepatitis E virus; Caliciviridae; Hepeviridae

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APA (6^th Edition):

Netzler, N. (2019). Broad-spectrum antivirals targeting viruses from the caliciviridae and hepeviridae. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/62685 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59105/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Netzler, Natalie. “Broad-spectrum antivirals targeting viruses from the caliciviridae and hepeviridae.” 2019. Doctoral Dissertation, University of New South Wales. Accessed April 17, 2021. http://handle.unsw.edu.au/1959.4/62685 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59105/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Netzler, Natalie. “Broad-spectrum antivirals targeting viruses from the caliciviridae and hepeviridae.” 2019. Web. 17 Apr 2021.

Vancouver:

Netzler N. Broad-spectrum antivirals targeting viruses from the caliciviridae and hepeviridae. [Internet] [Doctoral dissertation]. University of New South Wales; 2019. [cited 2021 Apr 17]. Available from: http://handle.unsw.edu.au/1959.4/62685 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59105/SOURCE02?view=true.

Council of Science Editors:

Netzler N. Broad-spectrum antivirals targeting viruses from the caliciviridae and hepeviridae. [Doctoral Dissertation]. University of New South Wales; 2019. Available from: http://handle.unsw.edu.au/1959.4/62685 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:59105/SOURCE02?view=true

Virginia Commonwealth University

4. Bhave, Sukhada. INVESTIGATING SYNERGY BETWEEN RIBONUCLEOTIDE REDUCTASE INHIBITORS AND CMV ANTIVIRALS.

Degree: MS, Microbiology & Immunology, 2012, Virginia Commonwealth University

URL: https://doi.org/10.25772/CNVY-TJ48 ; https://scholarscompass.vcu.edu/etd/2838

► Cytomegalovirus (CMV) infections remain a significant problem in congenitally infected infants and immunocompromised individuals. Modest antiviral activities of currently approved drugs coupled with dose-limiting toxicities… (more)

Subjects/Keywords: cytomegalovirus; antivirals; Medicine and Health Sciences

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APA (6^th Edition):

Bhave, S. (2012). INVESTIGATING SYNERGY BETWEEN RIBONUCLEOTIDE REDUCTASE INHIBITORS AND CMV ANTIVIRALS. (Thesis). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/CNVY-TJ48 ; https://scholarscompass.vcu.edu/etd/2838

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bhave, Sukhada. “INVESTIGATING SYNERGY BETWEEN RIBONUCLEOTIDE REDUCTASE INHIBITORS AND CMV ANTIVIRALS.” 2012. Thesis, Virginia Commonwealth University. Accessed April 17, 2021. https://doi.org/10.25772/CNVY-TJ48 ; https://scholarscompass.vcu.edu/etd/2838.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bhave, Sukhada. “INVESTIGATING SYNERGY BETWEEN RIBONUCLEOTIDE REDUCTASE INHIBITORS AND CMV ANTIVIRALS.” 2012. Web. 17 Apr 2021.

Vancouver:

Bhave S. INVESTIGATING SYNERGY BETWEEN RIBONUCLEOTIDE REDUCTASE INHIBITORS AND CMV ANTIVIRALS. [Internet] [Thesis]. Virginia Commonwealth University; 2012. [cited 2021 Apr 17]. Available from: https://doi.org/10.25772/CNVY-TJ48 ; https://scholarscompass.vcu.edu/etd/2838.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bhave S. INVESTIGATING SYNERGY BETWEEN RIBONUCLEOTIDE REDUCTASE INHIBITORS AND CMV ANTIVIRALS. [Thesis]. Virginia Commonwealth University; 2012. Available from: https://doi.org/10.25772/CNVY-TJ48 ; https://scholarscompass.vcu.edu/etd/2838

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat Autònoma de Barcelona

5. Chen, Qian. Caracterización molecular del perfil de resistencias del virus de la hepatitis C después del fallo terapéutico a antivirales de acción directa mediante secuenciación masiva.

Degree: Departament de Medicina, 2018, Universitat Autònoma de Barcelona

URL: http://hdl.handle.net/10803/666656

► Chronic hepatitis C infection is considered as a major public health issue worldwide due to its linkage to the development of advanced liver diseases and… (more)

▼ Chronic hepatitis C infection is considered as a major public health issue worldwide due to its linkage to the development of advanced liver diseases and hepatocellular carcinoma. Currently, the availability of highly efficient and well-tolerated antiviral therapies based on combinations of direct acting antivirals (DAAs) has provided sustained virological response (SVR) in nearly 95% of patients. Despite the excellent efficacy of DAAs, still a non-negligible percentage of patients do not achieve virological cure. At treatment failure, resistance-associated substitutions (RASs) are usually selected at high frequencies in the viral population. While selection of RASs has an important role in treatment failure, the clinical impact of RASs and its relevance in retreatment still remain unknown. Few real-life data on RASs testing are available, mainly performed by Sanger sequencing. In this PhD Thesis, we have performed a RASs analysis in a cohort of 220 patients who experienced treatment failure to several DAA combinations using next generation sequencing. In our analysis, the RASs profile that emerge after each DAA-based treatment was subtype-specific, which strongly suggests the use of subtype-specific primers to avoid amplification bias. Also, several high prevalent RASs combinations were characterized, suggesting the importance of their detection before retreatment due to their high level of resistance. Moreover, attending to the high occurrence of extra-target RASs detected, testing all genomic regions for RASs analysis is strongly recommended for treatment decision making. In summary, the high prevalence of RASs at treatment failure, the high amount of minority RASs and the combination of RASs at the same genome, reinforce the importance of RASs analysis before retreatment using ultra-deep sequencing in order to maximize SVR. The outcome of patients who undergo retreatment should be also analysed in order to characterize clinically meaningful RASs. Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Quer Sivila, Josep (director), Perales Viejo, Celia (director), Gregori i Font, Josep (director).

Subjects/Keywords: Hepatitis; Resistències; Resistencias; Resistance; Antivirals; Antivirales; Antivirals; Ciències de la Salut; 578

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APA (6^th Edition):

Chen, Q. (2018). Caracterización molecular del perfil de resistencias del virus de la hepatitis C después del fallo terapéutico a antivirales de acción directa mediante secuenciación masiva. (Thesis). Universitat Autònoma de Barcelona. Retrieved from http://hdl.handle.net/10803/666656

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Qian. “Caracterización molecular del perfil de resistencias del virus de la hepatitis C después del fallo terapéutico a antivirales de acción directa mediante secuenciación masiva.” 2018. Thesis, Universitat Autònoma de Barcelona. Accessed April 17, 2021. http://hdl.handle.net/10803/666656.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Qian. “Caracterización molecular del perfil de resistencias del virus de la hepatitis C después del fallo terapéutico a antivirales de acción directa mediante secuenciación masiva.” 2018. Web. 17 Apr 2021.

Vancouver:

Chen Q. Caracterización molecular del perfil de resistencias del virus de la hepatitis C después del fallo terapéutico a antivirales de acción directa mediante secuenciación masiva. [Internet] [Thesis]. Universitat Autònoma de Barcelona; 2018. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10803/666656.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen Q. Caracterización molecular del perfil de resistencias del virus de la hepatitis C después del fallo terapéutico a antivirales de acción directa mediante secuenciación masiva. [Thesis]. Universitat Autònoma de Barcelona; 2018. Available from: http://hdl.handle.net/10803/666656

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. Hadpech, Sudarat. Nouveaux agents antiviraux dérivés de protéines cellulaires à motifs répétés et ciblant l’assemblage du VIH : Application of Alpha-Repeat Proteins as Antiviral Molecules Against HIV-1 Targeting Viral Assembly or Maturation.

Degree: Docteur es, Biologie, 2017, Lyon; Mahāwitthayālai Chīang Mai

URL: http://www.theses.fr/2017LYSE1139

►

Au cours de notre programme de thèse, nous avons isolé et caractérisé des molécules protéiques à activité antivirale intracellulaire dirigée contre le VIH-1. Ces protéines,… (more)

▼

Au cours de notre programme de thèse, nous avons isolé et caractérisé des molécules protéiques à activité antivirale intracellulaire dirigée contre le VIH-1. Ces protéines, appelées aRep, ont été obtenues par criblage d'une banque de protéines artificielles de nouvelle génération, construites de faÃ§on combinatoire à partir de protéines naturelles constituées de motifs alpha-hélicoidaux répétés. La cible virale, ou "appât", utilisé pour ce criblage a été une région de la polyprotéine Gag du VIH-1 identifiée comme une cible privilégiée de nouvelles thérapeutiques antivirales, car essentielle à l'assemblage viral, l'empaquetage du génome viral et le clivage de maturation de Gag aboutissant à la formation de virions infectieux. Deux molécules d'aRep à affinité élevée pour la cible virale, l'aRep4E3 (32 kDa; 7 motifs répétés) et l'aRep9A8 (28 kDa; 6 motifs répétés) ont ainsi été identifiées, isolées et clonées. L'étude de l'activité anti-VIH intracellulaire de ces aRep a été réalisée dans différents systèmes d'expression cellulaire, nécessitant la construction de lignées stables de cellules d'insecte et de cellules épithéliales humaines, et leur infection par différents types de vecteurs viraux recombinants, baculovirus ou lentivirus, porteurs du gène rapporteur luciférase. Mais surtout, cette étude a été menée sur des cellules lymphocytaires-T (SupT1), cibles naturelles du virus, exprimant ces aRep et infectées par du VIH-1 naturel infectieux. Nos résultats ont montré que l'aRep4E3 et l'aRep9A8 ont toutes deux un effet négatif significatif sur le cycle réplicatif du VIH-1, mais ciblent des fonctions virales différentes. L'aRep4E3 bloque l'empaquetage du génome viral, tandis que l'aRep9A8 inhibe la maturation et diminue l'infectivité virale. De plus, l'aRep9A8, exprimée de façon constitutive dans les cellules SupT1, leur confère une résistance au VIH: une lignée de SupT1 chroniquement infectée par le VIH-1 a pu Ãªtre ainsi isolée et maintenue en culture pendant plusieurs semaines, sans effet cytopathique viro-induit apparent. Ces nouvelles données auront des implications non-négligeables dans le choix et la conduite de futures stratégies de thérapie cellulaire anti-VIH

HIV-1 infection is a long-term disease which required a long-life treatment. Besides the standard HAART regiment, HIV gene therapy is a promising alternative strategy which give rise to hope for the better HIV-1 treatment. Protein therapeutics is one another technique that represent high impact results in curing various types of disease. It is already become a significant part of current medical treatments. In this study we first designed aRep, a non-immunoglobulin scaffold protein which target two domains of HIV-1 Pr55Gag, SP1-NC and investigated their roles as an intracellular therapeutic agents. Phage display technology was used for the specific isolation of aRep against a critical C-terminal region of the HIV-1 Pr55Gag precursor from a large and diverse library. The antiviral activity of these two Pr55Gag binders was investigated using different…

Advisors/Committee Members: Hong, Saw-See (thesis director), Tayapiwatana, Chaitchaï (thesis director).

Subjects/Keywords: Antivirals; VIH-1; Protéines à motifs répétés; AlphaRep; Antivirals; HIV-1; Repeat proteins; AlphaRep; 572

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APA (6^th Edition):

Hadpech, S. (2017). Nouveaux agents antiviraux dérivés de protéines cellulaires à motifs répétés et ciblant l’assemblage du VIH : Application of Alpha-Repeat Proteins as Antiviral Molecules Against HIV-1 Targeting Viral Assembly or Maturation. (Doctoral Dissertation). Lyon; Mahāwitthayālai Chīang Mai. Retrieved from http://www.theses.fr/2017LYSE1139

Chicago Manual of Style (16^th Edition):

Hadpech, Sudarat. “Nouveaux agents antiviraux dérivés de protéines cellulaires à motifs répétés et ciblant l’assemblage du VIH : Application of Alpha-Repeat Proteins as Antiviral Molecules Against HIV-1 Targeting Viral Assembly or Maturation.” 2017. Doctoral Dissertation, Lyon; Mahāwitthayālai Chīang Mai. Accessed April 17, 2021. http://www.theses.fr/2017LYSE1139.

MLA Handbook (7^th Edition):

Hadpech, Sudarat. “Nouveaux agents antiviraux dérivés de protéines cellulaires à motifs répétés et ciblant l’assemblage du VIH : Application of Alpha-Repeat Proteins as Antiviral Molecules Against HIV-1 Targeting Viral Assembly or Maturation.” 2017. Web. 17 Apr 2021.

Vancouver:

Hadpech S. Nouveaux agents antiviraux dérivés de protéines cellulaires à motifs répétés et ciblant l’assemblage du VIH : Application of Alpha-Repeat Proteins as Antiviral Molecules Against HIV-1 Targeting Viral Assembly or Maturation. [Internet] [Doctoral dissertation]. Lyon; Mahāwitthayālai Chīang Mai; 2017. [cited 2021 Apr 17]. Available from: http://www.theses.fr/2017LYSE1139.

Council of Science Editors:

Hadpech S. Nouveaux agents antiviraux dérivés de protéines cellulaires à motifs répétés et ciblant l’assemblage du VIH : Application of Alpha-Repeat Proteins as Antiviral Molecules Against HIV-1 Targeting Viral Assembly or Maturation. [Doctoral Dissertation]. Lyon; Mahāwitthayālai Chīang Mai; 2017. Available from: http://www.theses.fr/2017LYSE1139

Universitat Pompeu Fabra

7. Fleta Soriano, Eric, 1983-. Broad-spectrum host-acting antivirals: identification and characterization of anti-HIV drugs.

Degree: Departament de Ciències Experimentals i de la Salut, 2015, Universitat Pompeu Fabra

URL: http://hdl.handle.net/10803/402212

► Cientos de factores del huésped relacionados con infecciones virales por VIH, hepatitis C, dengue o virus del Nilo occidental han sido identificados. Como muchos de… (more)

Subjects/Keywords: Broad-spectrum antivirals; Host-actings antivirals; HIV; Soraphen A; Ratjadone A; VIH; Antiiviral amplio aspectro; Antiviral contra hospedador; 578

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APA (6^th Edition):

Fleta Soriano, Eric, 1. (2015). Broad-spectrum host-acting antivirals: identification and characterization of anti-HIV drugs. (Thesis). Universitat Pompeu Fabra. Retrieved from http://hdl.handle.net/10803/402212

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fleta Soriano, Eric, 1983-. “Broad-spectrum host-acting antivirals: identification and characterization of anti-HIV drugs.” 2015. Thesis, Universitat Pompeu Fabra. Accessed April 17, 2021. http://hdl.handle.net/10803/402212.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fleta Soriano, Eric, 1983-. “Broad-spectrum host-acting antivirals: identification and characterization of anti-HIV drugs.” 2015. Web. 17 Apr 2021.

Vancouver:

Fleta Soriano, Eric 1. Broad-spectrum host-acting antivirals: identification and characterization of anti-HIV drugs. [Internet] [Thesis]. Universitat Pompeu Fabra; 2015. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10803/402212.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fleta Soriano, Eric 1. Broad-spectrum host-acting antivirals: identification and characterization of anti-HIV drugs. [Thesis]. Universitat Pompeu Fabra; 2015. Available from: http://hdl.handle.net/10803/402212

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Loyola University Chicago

8. Banach, Bridget. A Study of Human Coronavirus NL63: Characterization of Virus Replication, Targeting of Papain-Like Protease 2 by Antivirals and Probing Virus Mediated Innate Immune Antagonism.

Degree: PhD, Microbiology and Immunology, 2012, Loyola University Chicago

URL: https://ecommons.luc.edu/luc_diss_restrict/12

► Acute respiratory tract infections in humans are responsible for significant morbidity and mortality especially in children, elderly, and the immunocompromised. Virus infection is the… (more)

▼ Acute respiratory tract infections in humans are responsible for significant morbidity and mortality especially in children, elderly, and the immunocompromised. Virus infection is the primary cause of acute respiratory tract infections. Infection with coronaviruses can cause disease ranging from common colds to severe acute respiratory syndrome. Currently no coronavirus-specific antivirals are available. Patients are given symptomatic treatment, or are prescribed inappropriately antibiotics which do not target the underlying virus infection. The identification of specific inhibitors of coronaviruses or knowledge about how coronaviruses interact with the innate immune system could provide new avenues for developing therapeutics. I investigated the replication of human coronavirus NL63 (HCoV-NL63) in primary human airway epithelial cultures and characterized the activity of the viral papain-like protease 2 (PLP2) domain. Using quantitative real time PCR and imaging techniques I showed that HCoV-NL63 undergoes productive replication in the ciliated bronchial epithelial cells. To identify potential broad spectrum inhibitors of HCoVs, small molecule inhibitors of SARS-CoV were screened for cross-reactivity against HCoV-NL63 PLP2 and I identified a compound, GRL-0737, which blocks HCoV-NL63 with an EC₅₀ ~5µM. I also investigated HCoV-NL63 mediated antagonism of interferon-β (IFN-β) induction. I showed that HCoV-NL63 infection of bronchial epithelial cells results in a small, but measurable release of IFN-β by enzyme linked immunosorbent assay (ELISA). I confirmed that HCoV-NL63 PLP2 is an IFN-β antagonist, and abrogates the ability of the newly identified innate immune signaling protein STING (stimulator of interferon genes) to induce expression of an IRF-3 dependent luciferase reporter. Furthermore, using immunofluorescence I demonstrated that HCoV-NL63 non-structural protein 3 (viral protein in which PLP2 resides) co-localizes with STING suggesting that HCoV-NL63 PLP2 may be targeting STING activation of the IRF-3 arm of the type I IFN response to virus infection. This work demonstrates that HCoV-NL63 PLP2 plays an important role in evasion of the host immune response and that HCoV-NL63 replication can be disrupted by inhibitors of the PLP2 protease, making this protease an attractive target for antiviral treatments of coronavirus infection.

Subjects/Keywords: Antivirals; HCoV-NL63; human airway epithelium; immunofluorescence; PLP2; TEM; Virology

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APA (6^th Edition):

Banach, B. (2012). A Study of Human Coronavirus NL63: Characterization of Virus Replication, Targeting of Papain-Like Protease 2 by Antivirals and Probing Virus Mediated Innate Immune Antagonism. (Doctoral Dissertation). Loyola University Chicago. Retrieved from https://ecommons.luc.edu/luc_diss_restrict/12

Chicago Manual of Style (16^th Edition):

Banach, Bridget. “A Study of Human Coronavirus NL63: Characterization of Virus Replication, Targeting of Papain-Like Protease 2 by Antivirals and Probing Virus Mediated Innate Immune Antagonism.” 2012. Doctoral Dissertation, Loyola University Chicago. Accessed April 17, 2021. https://ecommons.luc.edu/luc_diss_restrict/12.

MLA Handbook (7^th Edition):

Banach, Bridget. “A Study of Human Coronavirus NL63: Characterization of Virus Replication, Targeting of Papain-Like Protease 2 by Antivirals and Probing Virus Mediated Innate Immune Antagonism.” 2012. Web. 17 Apr 2021.

Vancouver:

Banach B. A Study of Human Coronavirus NL63: Characterization of Virus Replication, Targeting of Papain-Like Protease 2 by Antivirals and Probing Virus Mediated Innate Immune Antagonism. [Internet] [Doctoral dissertation]. Loyola University Chicago; 2012. [cited 2021 Apr 17]. Available from: https://ecommons.luc.edu/luc_diss_restrict/12.

Council of Science Editors:

Banach B. A Study of Human Coronavirus NL63: Characterization of Virus Replication, Targeting of Papain-Like Protease 2 by Antivirals and Probing Virus Mediated Innate Immune Antagonism. [Doctoral Dissertation]. Loyola University Chicago; 2012. Available from: https://ecommons.luc.edu/luc_diss_restrict/12

9. Jesteadt, Eric Matthew Neff. USING THE INFLUENZA POLYMERASE 5'-ENDONUCLEASE ACTIVITY TO DEVELOP NOVEL siRNA THERAPEUTICS.

Degree: 2014, Johns Hopkins University

URL: http://jhir.library.jhu.edu/handle/1774.2/37266

► Influenza is a global public health burden, producing seasonal epidemics with 3-5 million severe cases and 250,000 to 500,000 deaths each year. In addition to… (more)

▼ Influenza is a global public health burden, producing seasonal epidemics with 3-5 million severe cases and 250,000 to 500,000 deaths each year. In addition to seasonal illness, influenza has also been responsible for global pandemics, the most notorious being the 1918 “Spanish Influenza.” While vaccination is the most useful tool for seasonal or pandemic influenza control, such interventions would not help individuals who are already infected. Antiviral drugs such as neuraminidase inhibitors and adamantanes can be effective if taken soon after symptoms appear, but antiviral resistance is developing. An alternative to antiviral drugs is the promising field of therapeutics based on RNA interference (RNAi). RNAi based treatments utilize chemically synthesized short interfering (si)RNAs between 21-24 nt in length to silence genes of interest. A number of research groups have investigated RNAi based antivirals, but the main limitations to their clinical use are risks of off-target effects and difficulty with appropriate dose delivery. A potential solution to both problems would be to use a pro-siRNA which is inert in uninfected cells but activated upon infection, thus limiting off-target effects to infected cells while sparing healthy cells. This approach would also provide dosing flexibility, as the active dose would be modulated by viral activity. In the case of influenza, a pro-siRNA consists of a standard siRNA duplex with a 10-13 nucleotide 7-methyl-guanosine (M7G) capped sequence on the 5’ end of the passenger or positive sense strand. This extension should render the pro-siRNA biologically inert in uninfected cells but be cleaved off in infected cells via PA mediated cap snatching activity, leaving behind a functional siRNA duplex. To test the feasibility of this approach, we designed variants of pro-siRNAs targeting eGFP, which can be expressed in a variety of cell types using transient or stable transfection. Cells were transfected with eGFP producing plasmids and/or siRNAs, infected with influenza 24-26 hours post transfection and fixed and analyzed 24 hours post infection. Through use of flow cytometry, we found that several pro-siRNA designs produced modest reductions in eGFP expression in infected cells, suggesting that the concept is feasible. However, further optimization will be required for capped pro-siRNAs to be a practical antiviral approach against seasonal and pandemic influenza. Advisors/Committee Members: Pekosz, Andrew S (advisor).

Subjects/Keywords: Influenza; RNAi; antivirals; therapeutics

…antivirals that can be used to control an infection. These are the neuraminidase inhibitors and the… …second class of antivirals, the adamantanes, includes amantadine and rimantadine (32)… …antivirals useless. RNA interference and the basics of RNAi therapeutics An attractive alternative… …to antivirals is the development of treatments based on the mechanism of RNA interference… …vectors expressing shRNAs (50). RNA interference-based antivirals against Respiratory…

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jesteadt, E. M. N. (2014). USING THE INFLUENZA POLYMERASE 5'-ENDONUCLEASE ACTIVITY TO DEVELOP NOVEL siRNA THERAPEUTICS. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37266

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jesteadt, Eric Matthew Neff. “USING THE INFLUENZA POLYMERASE 5'-ENDONUCLEASE ACTIVITY TO DEVELOP NOVEL siRNA THERAPEUTICS.” 2014. Thesis, Johns Hopkins University. Accessed April 17, 2021. http://jhir.library.jhu.edu/handle/1774.2/37266.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jesteadt, Eric Matthew Neff. “USING THE INFLUENZA POLYMERASE 5'-ENDONUCLEASE ACTIVITY TO DEVELOP NOVEL siRNA THERAPEUTICS.” 2014. Web. 17 Apr 2021.

Vancouver:

Jesteadt EMN. USING THE INFLUENZA POLYMERASE 5'-ENDONUCLEASE ACTIVITY TO DEVELOP NOVEL siRNA THERAPEUTICS. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2021 Apr 17]. Available from: http://jhir.library.jhu.edu/handle/1774.2/37266.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jesteadt EMN. USING THE INFLUENZA POLYMERASE 5'-ENDONUCLEASE ACTIVITY TO DEVELOP NOVEL siRNA THERAPEUTICS. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37266

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Perrier, Anabelle. Etude du trafic intracellulaire de la protéine M du coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV) : Intracellular trafficking of the M protein of Middle East respiratory syndrome coronavirus (MERS-CoV).

Degree: Docteur es, Biochimie, biologie cellulaire et moléculaire, physiologie et nutrition, 2019, Université Lille II – Droit et Santé

URL: http://www.theses.fr/2019LIL2S018

►

Les coronavirus sont une famille de virus émergents, comme l’ont montré les émergences récentes des coronavirus SARS-CoV (Severe acute respiratory syndrome coronavirus) et MERS-CoV (Middle-East… (more)

▼

Les coronavirus sont une famille de virus émergents, comme l’ont montré les émergences récentes des coronavirus SARS-CoV (Severe acute respiratory syndrome coronavirus) et MERS-CoV (Middle-East respiratory syndrome coronavirus), pathogènes pour l’homme. Nous ne disposons ni d’antiviraux spécifiques ni de vaccins pour lutter contre les coronavirus.Des quatre protéines structurales du virus, la protéine M est le moteur de l’assemblage viral. Exprimée seule en cellules, elle peut dépasser le site d’assemblage dans la voie de sécrétion. Nous avons confirmé la localisation de MERS-M dans le TGN(trans-golgi network) et identifié deux signaux dans son domaine C-terminal impliqués dans son trafic : un signal DxE d’export du réticulum, et un signal KxGxYR de rétention dans le TGN. Le signal DxE avait déjà été identifié sur une autre protéine virale, tandis que le signal KxGxYR est un nouveau motif. Pour confirmer son rôle nous avons construit des chimères entre MERS-M et la protéine M du coronavirus IBV (Infectious bronchitis virus), localisée dans le compartiment intermédiaire entre le RE et le Golgi (ERGIC), et démontré que pour les deux protéines le domaine C-terminal est déterminant pour leur localisation spécifique.Un second projet de caractérisation de l’activité antivirale de la digoxigénine contre le HCoV-229E a été initié. Nous avons démontré que cette drogue inhibe le virus à une étape post-entrée, avec une concentration inhibitrice médiane (IC50) de 250nM, et qu’elle n’est pas toxique pour les cellules à cette concentration. Elle inhibe aussi l’infection par le virus de l’hépatite C, et elle semble cibler une étape précoce de la réplication des virus RNA (+).

Coronaviruses are an important family of emerging pathogens, as shown by therecent emergence of pathogenic SARS-CoV (Severe acute respiratory syndromecoronavirus) and MERS-CoV (Middle-East respiratory syndrome coronavirus) in the lasttwo decades. There are still some knowledge gaps concerning the biology ofcoronaviruses and we do not have any specific treatment or vaccine.Among the four structural proteins of the virus, the M protein is considered to bethe motor of viral assembly. Expressed alone in cells, M proteins can go beyond theassembly site of the virus (Endoplasmic reticulum-Golgi intermediate compartment,ERGIC) in the secretory pathway. We confirmed MERS-M localization in the Trans-Golginetwork (TGN) and identified two signals involved in its intracellular trafficking in its Cterminaldomain: a DxE ER export signal, and a KxGxYR TGN retention signal. The DxEsignal was already identified on another viral protein, whereas the KxGxYR signal is anew motif. To confirm the role of KxGxYR signal in TGN retention, we constructedchimeras between MERS-M and the protein M of the Infectious bronchitis virus (IBV),located in the ERGIC. Our results suggest that for both MERS-M and IBV-M the Cterminaldomain is determinant for the specific localization of the proteins.We also initiated a project on the characterization of the antiviral activity ofdigoxigenin…

Advisors/Committee Members: Belouzard, Sandrine (thesis director).

Subjects/Keywords: Antiviraux; Trafic intracellulaire; Protéine M; Intracellular trafficking; Antivirals; M protein

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Perrier, A. (2019). Etude du trafic intracellulaire de la protéine M du coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV) : Intracellular trafficking of the M protein of Middle East respiratory syndrome coronavirus (MERS-CoV). (Doctoral Dissertation). Université Lille II – Droit et Santé. Retrieved from http://www.theses.fr/2019LIL2S018

Chicago Manual of Style (16^th Edition):

Perrier, Anabelle. “Etude du trafic intracellulaire de la protéine M du coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV) : Intracellular trafficking of the M protein of Middle East respiratory syndrome coronavirus (MERS-CoV).” 2019. Doctoral Dissertation, Université Lille II – Droit et Santé. Accessed April 17, 2021. http://www.theses.fr/2019LIL2S018.

MLA Handbook (7^th Edition):

Perrier, Anabelle. “Etude du trafic intracellulaire de la protéine M du coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV) : Intracellular trafficking of the M protein of Middle East respiratory syndrome coronavirus (MERS-CoV).” 2019. Web. 17 Apr 2021.

Vancouver:

Perrier A. Etude du trafic intracellulaire de la protéine M du coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV) : Intracellular trafficking of the M protein of Middle East respiratory syndrome coronavirus (MERS-CoV). [Internet] [Doctoral dissertation]. Université Lille II – Droit et Santé 2019. [cited 2021 Apr 17]. Available from: http://www.theses.fr/2019LIL2S018.

Council of Science Editors:

Perrier A. Etude du trafic intracellulaire de la protéine M du coronavirus du syndrome respiratoire du Moyen-Orient (MERS-CoV) : Intracellular trafficking of the M protein of Middle East respiratory syndrome coronavirus (MERS-CoV). [Doctoral Dissertation]. Université Lille II – Droit et Santé 2019. Available from: http://www.theses.fr/2019LIL2S018

University of Manitoba

11. Cook, Bradley William Michael. Developing Antiviral Platforms And Assessing Interferon Against Kyasanur Forest Disease Virus.

Degree: Microbiology, 2015, University of Manitoba

URL: http://hdl.handle.net/1993/30913

► Kyasanur Forest disease virus (KFDV) of the Flaviviridae virus family has caused seasonal infections and periodic outbreaks in Karnataka, India. First identified in 1957, KFDV… (more)

▼ Kyasanur Forest disease virus (KFDV) of the Flaviviridae virus family has caused seasonal infections and periodic outbreaks in Karnataka, India. First identified in 1957, KFDV annually infects 400-500 people and has a fatality rate of 3-5%; there are no approved antivirals and the existing licensed vaccine’s effectiveness appears to be questionable. Many tools for KFDV research are limited and this work sought to develop methods for analysing antivirals, including interferon (IFN)-α/β species. The BHK-21 (ATCC) cell line allowed for high virus propagation and distinguishable cytopathic effects (CPE) for determining antiviral effectiveness. The additional tool of a reverse genetics system expressing a full-length cDNA KFDV genome with a GFP reporter failed to propagate, despite numerous GFP genome-insertion strategies. The clinically approved IFN-α2a or IFN-α2b has had variable success at combatting flavivirus diseases in people, especially in the immuno-compromised. The continued passaging of KFDV-infected cells with repeated IFN-α2a treatment did not eliminate KFDV and had little effect on infectious particle production. IFN-αspecies, αWA and α were more effective than IFN-α2a and α2b at reducing KFDV; however dose ranges indicated that while low concentrations could limit CPE, higher concentrations were needed to inhibit virion release. Avoidance of IFN-α/β through Jak/STAT signalling repression was attributed to the NS5 protein, specifically the RdRp domain based on data obtained with luciferase and vesicular stomatitis virus (VSV) recovery assays. However, the mechanism appears to act subsequently to STAT1/2 activation without NS5 binding to any Jak/STAT components. A non-infectious, replicative system serving as a platform for antiviral drug testing against KFDV in a high throughput manner could only provide luciferase signals when the NS proteins capable of driving replication, were supplied in cis (subgenomic) but not in trans (antigenome). To conclude, IFN-α species such as IFN-αWA may be better suited than the licensed IFN-α2a for treatment of KFDV infections; however, IFN effects appear to be subdued in vitro due to the actions of the NS5 protein. While IFN may not be a successful antiviral against KFDV, the work in this thesis provides a foundation for evaluating other potential anti-KFDV therapeutics. Advisors/Committee Members: Theriault, Steven (Microbiology) Court, Deborah (Microbiology) (supervisor), de Kievit, Teresa (Microbiology) Kobasa, Darwyn (Medical Microbiology) Holbrook, Michael (United States Army Medical Research Institute of Infectious Diseases) (examiningcommittee).

Subjects/Keywords: Flavivirus; Tick-borne flavivirus; Interferon; Molecular biology; Antivirals; Hemorrhagic fever virus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cook, B. W. M. (2015). Developing Antiviral Platforms And Assessing Interferon Against Kyasanur Forest Disease Virus. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/30913

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cook, Bradley William Michael. “Developing Antiviral Platforms And Assessing Interferon Against Kyasanur Forest Disease Virus.” 2015. Thesis, University of Manitoba. Accessed April 17, 2021. http://hdl.handle.net/1993/30913.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cook, Bradley William Michael. “Developing Antiviral Platforms And Assessing Interferon Against Kyasanur Forest Disease Virus.” 2015. Web. 17 Apr 2021.

Vancouver:

Cook BWM. Developing Antiviral Platforms And Assessing Interferon Against Kyasanur Forest Disease Virus. [Internet] [Thesis]. University of Manitoba; 2015. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/1993/30913.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cook BWM. Developing Antiviral Platforms And Assessing Interferon Against Kyasanur Forest Disease Virus. [Thesis]. University of Manitoba; 2015. Available from: http://hdl.handle.net/1993/30913

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

12. Bekking, Christian. Assessment of Bioaerosol Samplers for the Detection and Quantification of Influenza Virus and Compounds that Potentially Influence Influenza Virus Replication.

Degree: 2018, University of Toronto

URL: http://hdl.handle.net/1807/102815

►

Bioaerosol samplers are used to detect and characterize influenza virus bioaerosols but current guidelines for sampler selection are lacking. We examined four bioaerosol samplers using… (more)

Subjects/Keywords: Antivirals; Bioaerosols; Bioaerosol samplers; Cardiac glycosides; Emission; Influenza; 0720

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bekking, C. (2018). Assessment of Bioaerosol Samplers for the Detection and Quantification of Influenza Virus and Compounds that Potentially Influence Influenza Virus Replication. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/102815

Chicago Manual of Style (16^th Edition):

Bekking, Christian. “Assessment of Bioaerosol Samplers for the Detection and Quantification of Influenza Virus and Compounds that Potentially Influence Influenza Virus Replication.” 2018. Masters Thesis, University of Toronto. Accessed April 17, 2021. http://hdl.handle.net/1807/102815.

MLA Handbook (7^th Edition):

Bekking, Christian. “Assessment of Bioaerosol Samplers for the Detection and Quantification of Influenza Virus and Compounds that Potentially Influence Influenza Virus Replication.” 2018. Web. 17 Apr 2021.

Vancouver:

Bekking C. Assessment of Bioaerosol Samplers for the Detection and Quantification of Influenza Virus and Compounds that Potentially Influence Influenza Virus Replication. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/1807/102815.

Council of Science Editors:

Bekking C. Assessment of Bioaerosol Samplers for the Detection and Quantification of Influenza Virus and Compounds that Potentially Influence Influenza Virus Replication. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/102815

University of Georgia

13. Carter, Leah D.b. Who gets the cure?.

Degree: 2017, University of Georgia

URL: http://hdl.handle.net/10724/36636

► Using the Hepatitis C Virus (HCV) as a focal point and newly approved Direct-Acting Antivirals as the impetus for change, this thesis explores the course… (more)

Subjects/Keywords: Regulatory Affairs; Medicaid; Hepatitis C; Direct-Acting Antivirals; Ryan White

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APA (6^th Edition):

Carter, L. D. b. (2017). Who gets the cure?. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/36636

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Carter, Leah D b. “Who gets the cure?.” 2017. Thesis, University of Georgia. Accessed April 17, 2021. http://hdl.handle.net/10724/36636.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Carter, Leah D b. “Who gets the cure?.” 2017. Web. 17 Apr 2021.

Vancouver:

Carter LDb. Who gets the cure?. [Internet] [Thesis]. University of Georgia; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10724/36636.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Carter LDb. Who gets the cure?. [Thesis]. University of Georgia; 2017. Available from: http://hdl.handle.net/10724/36636

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Sydney

14. Swaminathan, Kavya. Novel anthocyanin inhibitors to influenza neuraminidase and monitioring antiviral resistance by mass spectrometry .

Degree: 2013, University of Sydney

URL: http://hdl.handle.net/2123/10220

► A novel matrix assisted laser desorption ionization (MALDI) mass spectrometry based approach to study the binding of inhibitors to the influenza virus neuraminidase is described.… (more)

Subjects/Keywords: Influenza; Antivirals; MassTrees; Anthocyanin; Drug resistance; Mass spectrometry

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APA (6^th Edition):

Swaminathan, K. (2013). Novel anthocyanin inhibitors to influenza neuraminidase and monitioring antiviral resistance by mass spectrometry . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/10220

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Swaminathan, Kavya. “Novel anthocyanin inhibitors to influenza neuraminidase and monitioring antiviral resistance by mass spectrometry .” 2013. Thesis, University of Sydney. Accessed April 17, 2021. http://hdl.handle.net/2123/10220.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Swaminathan, Kavya. “Novel anthocyanin inhibitors to influenza neuraminidase and monitioring antiviral resistance by mass spectrometry .” 2013. Web. 17 Apr 2021.

Vancouver:

Swaminathan K. Novel anthocyanin inhibitors to influenza neuraminidase and monitioring antiviral resistance by mass spectrometry . [Internet] [Thesis]. University of Sydney; 2013. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/2123/10220.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Swaminathan K. Novel anthocyanin inhibitors to influenza neuraminidase and monitioring antiviral resistance by mass spectrometry . [Thesis]. University of Sydney; 2013. Available from: http://hdl.handle.net/2123/10220

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales

15. Eltahla, Auda Abdelsalam. Non-nucleoside inhibitors of viral RNA polymerases; scaffolds for rational drug design.

Degree: Biotechnology & Biomolecular Sciences, 2014, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/53565 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12262/SOURCE02?view=true

► The hepatitis C virus (HCV) and norovirus (NoV) are significant human pathogens posing a substantial health and economic burden in both developing and developed countries.… (more)

▼ The hepatitis C virus (HCV) and norovirus (NoV) are significant human pathogens posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of these viruses through the development of both vaccines and antivirals has proven to be difficult, partly because of the refractoriness in growing these viruses in cell culture. The current standard treatment for HCV is expensive, poorly tolerated, has a long duration, and is only partly effective. Although new direct-acting antivirals (DAA) are entering clinical treatment, these emerging molecules have been mainly targeted against one of six HCV genotypes, namely G1. Conversely, there are no antivirals for the treatment of chronic NoV infections, or for use as a prophylactic measure in an outbreak setting, which typically affects hospitals, nursing homes and other enclosed environments. The viral RNA-dependent RNA polymerases (RdRp) of HCV and NoV are prime targets for antiviral development, given their crucial role for the viral replication, and the absence of a homologous human enzyme. This study describes the discovery and characterisation of the first non-nucleoside inhibitors (NNI) specifically targeted against the RdRp of HCV G3a, a neglected but increasingly important genotype of HCV. Chemical scaffolds and derivatives were identified with low micromolar inhibitory activity against recombinant RdRp, and the HCV replicon cell culture model. Furthermore, the efficacy of previously identified inhibitors against the HCV G3a RdRp was examined, and a novel mechanism of enhancement of de novo transcription was discovered for a subclass of these antivirals; the T2 and P-β binding NNIs. This study also describes the high-throughput identification of the first four NoV-directed NNI scaffolds, which provide a strong platform for future rational drug design for antivirals against another pathogen with thus far limited control measures Advisors/Committee Members: White, Peter, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW, Eden, John-Sebastian, Marie Bashir Institute for Infectious Diseases & Biosecurity, School of Biological Sciences and Sydney Medical School, University of Sydney, Camperdown, NSW, Australia, Bull, Rowena, Medical Sciences, Faculty of Medicine, UNSW.

Subjects/Keywords: RNA-dependent RNA polymerase; Hepatitis C virus; Norovirus; Antivirals

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Eltahla, A. A. (2014). Non-nucleoside inhibitors of viral RNA polymerases; scaffolds for rational drug design. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53565 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12262/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Eltahla, Auda Abdelsalam. “Non-nucleoside inhibitors of viral RNA polymerases; scaffolds for rational drug design.” 2014. Doctoral Dissertation, University of New South Wales. Accessed April 17, 2021. http://handle.unsw.edu.au/1959.4/53565 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12262/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Eltahla, Auda Abdelsalam. “Non-nucleoside inhibitors of viral RNA polymerases; scaffolds for rational drug design.” 2014. Web. 17 Apr 2021.

Vancouver:

Eltahla AA. Non-nucleoside inhibitors of viral RNA polymerases; scaffolds for rational drug design. [Internet] [Doctoral dissertation]. University of New South Wales; 2014. [cited 2021 Apr 17]. Available from: http://handle.unsw.edu.au/1959.4/53565 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12262/SOURCE02?view=true.

Council of Science Editors:

Eltahla AA. Non-nucleoside inhibitors of viral RNA polymerases; scaffolds for rational drug design. [Doctoral Dissertation]. University of New South Wales; 2014. Available from: http://handle.unsw.edu.au/1959.4/53565 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12262/SOURCE02?view=true

Queen Mary, University of London

16. Wing, Peter Alexander Cornelius. Reduced sensitivity of Genotype 3 hepatitis C virus to direct acting antivirals.

Degree: PhD, 2018, Queen Mary, University of London

URL: http://qmro.qmul.ac.uk/xmlui/handle/123456789/44044 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766210

► Sofosbuvir is a uridine based nucleotide inhibitor of the hepatitis C viral (HCV) polymerase that is the backbone of many treatment regimens. In combination with… (more)

Subjects/Keywords: 616.3; HEPATITIS C VIRUS; Antivirals; sofosbuvir; Genotype 3 HCV

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wing, P. A. C. (2018). Reduced sensitivity of Genotype 3 hepatitis C virus to direct acting antivirals. (Doctoral Dissertation). Queen Mary, University of London. Retrieved from http://qmro.qmul.ac.uk/xmlui/handle/123456789/44044 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766210

Chicago Manual of Style (16^th Edition):

Wing, Peter Alexander Cornelius. “Reduced sensitivity of Genotype 3 hepatitis C virus to direct acting antivirals.” 2018. Doctoral Dissertation, Queen Mary, University of London. Accessed April 17, 2021. http://qmro.qmul.ac.uk/xmlui/handle/123456789/44044 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766210.

MLA Handbook (7^th Edition):

Wing, Peter Alexander Cornelius. “Reduced sensitivity of Genotype 3 hepatitis C virus to direct acting antivirals.” 2018. Web. 17 Apr 2021.

Vancouver:

Wing PAC. Reduced sensitivity of Genotype 3 hepatitis C virus to direct acting antivirals. [Internet] [Doctoral dissertation]. Queen Mary, University of London; 2018. [cited 2021 Apr 17]. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/44044 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766210.

Council of Science Editors:

Wing PAC. Reduced sensitivity of Genotype 3 hepatitis C virus to direct acting antivirals. [Doctoral Dissertation]. Queen Mary, University of London; 2018. Available from: http://qmro.qmul.ac.uk/xmlui/handle/123456789/44044 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.766210

17. O'Rourke, Aubrie. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores.

Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2015, King Abdullah University of Science and Technology

URL: http://hdl.handle.net/10754/552842

► Natural products offer many possibilities for the treatment of disease. More than 70% of the Earth’s surface is ocean, and recent exploration and access has… (more)

Subjects/Keywords: Antivirals; Red Sea; Sponges; West Nile Virus; HIV-I; Natural products

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APA (6^th Edition):

O'Rourke, A. (2015). Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/552842

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

O'Rourke, Aubrie. “Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores.” 2015. Thesis, King Abdullah University of Science and Technology. Accessed April 17, 2021. http://hdl.handle.net/10754/552842.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

O'Rourke, Aubrie. “Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores.” 2015. Web. 17 Apr 2021.

Vancouver:

O'Rourke A. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2015. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/10754/552842.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

O'Rourke A. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores. [Thesis]. King Abdullah University of Science and Technology; 2015. Available from: http://hdl.handle.net/10754/552842

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

18. Batista, Mariana Nogueira. Avaliação de peptídeos sintéticos na inibição direcionada do vírus da hepatite C.

Degree: 2018, Universidade Estadual Paulista (UNESP)

URL: http://hdl.handle.net/11449/154951

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Submitted by Mariana Nogueira Batista ([email protected]) on 2018-08-11T13:03:25Z No. of bitstreams: 1 Tese Doutorado_Mariana_final.pdf: 7344224 bytes, checksum: 55aafb62a666837e6ce68354b806d8af (MD5)

Rejected by Elza Mitiko Sato null… (more)

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Submitted by Mariana Nogueira Batista ([email protected]) on 2018-08-11T13:03:25Z No. of bitstreams: 1 Tese Doutorado_Mariana_final.pdf: 7344224 bytes, checksum: 55aafb62a666837e6ce68354b806d8af (MD5)

Rejected by Elza Mitiko Sato null ([email protected]), reason: Solicitamos que realize correções na submissão seguindo as orientações abaixo: 01) Como você recebeu financiamento da CAPES, o nome dela deve constar também na FOLHA DE ROSTO e de APROVAÇÃO. Ex.: Financiadoras : FAPESP – Proc: 2016/02174-4 CAPES 02)Na folha de APROVAÇÃO colocar as duas financiadoras e no caso da FAPESP também o número do processo. 03) O resumo e abstract não estão na ordem correta; a ordem correta das páginas pré-textuais: capa, folha de rosto, ficha catalográfica, folha de aprovação, dedicatória, agradecimentos, epígrafe, resumo na língua vernácula, resumo em língua estrangeira e sumário. 04) As páginas 124 e 137 estão em branco, o arquivo não pode conter páginas em branco. 05) No sumário o capítulo I consta na página 20 e no texto ele está na página 21. 06) As REFERÊNCIAS BIBLIOGRÁFICAS que constam na página 49 seriam as referências gerais da tese ou apenas do capítulo I ? 07) A sua tese está dividida em 04(quatro) capítulos; no sumário falta na indicação dos capítulos OBS:-Estou encaminhando via e-mail o template/modelo das páginas pré-textuais para que você possa fazer as correções, sugerimos que siga este modelo pois ele contempla as normas da ABNT Lembramos que o arquivo depositado no repositório deve ser igual ao impresso, o rigor com o padrão da Universidade se deve ao fato de que o seu trabalho passará a ser visível mundialmente. Agradecemos a compreensão. on 2018-08-13T18:52:30Z (GMT)

Submitted by Mariana Nogueira Batista ([email protected]) on 2018-08-16T19:14:01Z No. of bitstreams: 1 Tese Doutorado_Mariana_final_Repositório.pdf: 7331796 bytes, checksum: 58221342a38ce66a3aac3483844d50a6 (MD5)

Rejected by Elza Mitiko Sato null ([email protected]), reason: Solicitamos que realize correções na submissão seguindo as orientações abaixo: No SUMÁRIO Problema 01) Deve ser retirada a citação : Fonte: Adaptada de Wyles et al., 2009 e de Tscherne et al., 2006 ................................ 36 Problema 02) Onde está escrito “Capítulo II - Artigo I ” você deve transcrever na frente também o título do artigo conforme está no texto. E também onde está “Capítulo II - Artigo II “ Lembramos que o arquivo depositado no repositório deve ser igual ao impresso, o rigor com o padrão da Universidade se deve ao fato de que o seu trabalho passará a ser visível mundialmente. Agradecemos a compreensão. on 2018-08-17T12:44:54Z (GMT)

Submitted by Mariana Nogueira Batista ([email protected]) on 2018-08-27T01:14:39Z No. of bitstreams: 1 Tese Doutorado_Mariana_final_Repositório.pdf: 7330679 bytes, checksum: 39d49c3a1d3675d0c03801538fc7c12c (MD5)

Approved for entry into…

Advisors/Committee Members: Universidade Estadual Paulista (UNESP), Rahal, Paula [UNESP], Carneiro, Bruno Moreira, Cilli, Eduardo Maffud [UNESP].

Subjects/Keywords: HCV; Pró-fármaco; Antivirais; Hecate; GA-Hecate; Lipid droplets; Prodrug; Antivirals

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Batista, M. N. (2018). Avaliação de peptídeos sintéticos na inibição direcionada do vírus da hepatite C. (Doctoral Dissertation). Universidade Estadual Paulista (UNESP). Retrieved from http://hdl.handle.net/11449/154951

Chicago Manual of Style (16^th Edition):

Batista, Mariana Nogueira. “Avaliação de peptídeos sintéticos na inibição direcionada do vírus da hepatite C.” 2018. Doctoral Dissertation, Universidade Estadual Paulista (UNESP). Accessed April 17, 2021. http://hdl.handle.net/11449/154951.

MLA Handbook (7^th Edition):

Batista, Mariana Nogueira. “Avaliação de peptídeos sintéticos na inibição direcionada do vírus da hepatite C.” 2018. Web. 17 Apr 2021.

Vancouver:

Batista MN. Avaliação de peptídeos sintéticos na inibição direcionada do vírus da hepatite C. [Internet] [Doctoral dissertation]. Universidade Estadual Paulista (UNESP); 2018. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/11449/154951.

Council of Science Editors:

Batista MN. Avaliação de peptídeos sintéticos na inibição direcionada do vírus da hepatite C. [Doctoral Dissertation]. Universidade Estadual Paulista (UNESP); 2018. Available from: http://hdl.handle.net/11449/154951

19. Sindac, Janice A. Development of Small Molecule Replication Inhibitors Against Western Equine Encephalitis Virus.

Degree: PhD, Medicinal Chemistry, 2014, University of Michigan

URL: http://hdl.handle.net/2027.42/110326

► Arborviruses such as western equine encephalitis virus (WEEV) are capable of causing a wide range of diseases in humans. The CDC and NIAID consider WEEV… (more)

▼ Arborviruses such as western equine encephalitis virus (WEEV) are capable of causing a wide range of diseases in humans. The CDC and NIAID consider WEEV as a potential bioterrorism weapon due to several factors: potential for aerosol transmission, lack of effective countermeasures, and ease of genetic manipulation to increase virulence and high levels of death. A series of thieno[3,2-b]pyrrole-based inhibitors were discovered to be active against WEEV following a high-throughput screen (HTS). This dissertation discusses the development of novel indole-2-carboxamide RNA replication inhibitors with improved in vitro and in vivo activity and the development of tag-free photoaffinity probes for target identification. A first-generation indole, CCG 203926 (12), with modestly improved potency and metabolic stability over the original screening lead CCG 32091, achieved efficacy in a preliminary in vivo study against neuroadapted Sindbis virus. Second-generation inhibitor, CCG 205432 (50), was the first inhibitor with submicromolar activity and further improved half-life compared to CCG-203926. In a WEEV-infected mouse model, in which CCG 203926 was inactive, it increased survival and decreased disease severity. Even though a related third generation inhibitor, CCG 209023 (110), was less potent than 50, it had a significantly improved half-life, lower recognition by Pgp and equal efficacy to CCG-205432 at improving survival. It was determined that 50 and related indole-2-carboxamide inhibitors have a wide range of activity against other RNA viruses and elicit their antiviral activity by targeting host factors instead of viral enzymatic proteins. One of the two photoaffinity probes, 126, is equipotent to lead indole 50 and is currently being used for preliminary target identification studies. Compound 110 is also being studied as a combination therapy with neuroprotective agents. The lack of clinical therapeutics against alphaviruses emphasizes the significance of this work, as there is a critical need to develop potent antivirals against these pathogens. Advisors/Committee Members: Larsen, Scott D. (committee member), Miller, David (committee member), Neubig, Richard Robert (committee member), Mosberg, Henry I. (committee member).

Subjects/Keywords: alphavirus; antivirals; Biological Chemistry; Science

…emphasizes the significance of this work, as there is a critical need to develop potent antivirals… …the CNS emphasizes the need for antivirals to prevent viral replication and neuroprotective…

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APA (6^th Edition):

Sindac, J. A. (2014). Development of Small Molecule Replication Inhibitors Against Western Equine Encephalitis Virus. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/110326

Chicago Manual of Style (16^th Edition):

Sindac, Janice A. “Development of Small Molecule Replication Inhibitors Against Western Equine Encephalitis Virus.” 2014. Doctoral Dissertation, University of Michigan. Accessed April 17, 2021. http://hdl.handle.net/2027.42/110326.

MLA Handbook (7^th Edition):

Sindac, Janice A. “Development of Small Molecule Replication Inhibitors Against Western Equine Encephalitis Virus.” 2014. Web. 17 Apr 2021.

Vancouver:

Sindac JA. Development of Small Molecule Replication Inhibitors Against Western Equine Encephalitis Virus. [Internet] [Doctoral dissertation]. University of Michigan; 2014. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/2027.42/110326.

Council of Science Editors:

Sindac JA. Development of Small Molecule Replication Inhibitors Against Western Equine Encephalitis Virus. [Doctoral Dissertation]. University of Michigan; 2014. Available from: http://hdl.handle.net/2027.42/110326

20. Aillot, Ludovic. Effets antiviraux de l'agonisation des Toll-like Récepteurs dans les cellules du foie, une nouvelle stratégie immunothérapeutique dans la lutte contre HBV : Antiviral effects by Toll-like receptors agonisation in liver cells, a new immunotherapeuticstrategy in the fight against HBV.

Degree: Docteur es, Infectiologie, 2018, Lyon

URL: http://www.theses.fr/2018LYSE1139

► Le virus de l'hépatite B (HBV) infecte chroniquement près de 240 millions d'individus dans le monde. L'infection chronique par HBV est un souci de santé… (more)

▼ Le virus de l'hépatite B (HBV) infecte chroniquement près de 240 millions d'individus dans le monde. L'infection chronique par HBV est un souci de santé publique majeur puisque l'infection peut évoluer au cours du temps vers la cirrhose et/ou l'hépatocarcinome (CHC). Malgré l'existence de traitements efficaces à base d'analogues de nucléos(t)ides permettant de diminuer la charge virale chez les patients, ceux-ci nécessitent une prise médicamenteuse à vie. En effet, malgré la diminution importante du risque de développer un cancer du foie, ces traitements ne permettent pas l'élimination définitive du virus. Les cellules infectées par HBV sont les hépatocytes du foie, qui remplissent la majorité des rôles vitaux de cet organe. La formation d'un minichromosome viral au sein de ces cellules infectées appelés ADNccc (pour ADN circulaire-covalemment-clos), est majoritairement responsable de la persistance du HBV. Les traitements actuels utilisés sont principalement des analogues de nucléos(t)ides et ceux-ci n'ont pas ou peu d'effets sur l'ADNccc. La nécessité de développer de nouvelles stratégies antivirales visant à éliminer définitivement HBV a donc conduit de nombreux laboratoires, dont le nôtre, à étudier l'utilisation de stratégies immuno-thérapeutiques incluant des stimulateurs de l'immunité innée (agonistes de TLR7, TLR8, RIG-1.) dans le cadre d'infections chroniques. De nombreuses études ont démontré que l'utilisation de ligands stimulant les récepteurs de l'immunité innée promouvait un fort effet antiviral, médié par la production endogène et locale de cytokines pro-inflammatoires et l'induction de gènes régulés par l'interféron (1SG). Dans ce but, nous nous sommes intéressés plus particulièrement aux potentiels effets antiviraux de l'agonisation des senseurs de l'immunité innée les plus connus, les Toll-like récepteurs (TLR), dans le cadre de l'infection par HBV dans les cellules hépatiques. La stratégie immuno-thérapeutique envisagée, vise à stimuler aussi bien les cellules immunitaires que les hépatocytes infectés. La caractérisation de l'expression de différents senseurs de l'immunité innée, d'une part dans les cellules primaires isolées du foie et d'autre part dans certaines lignées cellulaires correspondantes, nous a permis d'avoir une vue d'ensemble 1) des récepteurs exprimés par les différentes cellules du foie notamment dans les hépatocytes (TLR2/TLR3/TLR4/TLR5) ; 2) d'évaluer la fonctionnalité de ceux-ci pour la production de cytokines (IL-6 ; IP-10) lors de leur agonisation 3) d'évaluer les modèles disponibles parmi les lignées cellulaires les plus proches immunologiquement des cellules hépatiques. Les cellules HepaRG et une nouvelle lignée dérivée des macrophages du foie les iKC par exemple sont plus proches respectivement des hépatocytes et des macrophages primaires hépatiques et sont donc des modèles relevant pour les études immuno-thérapeutiques. L'utilisation de ligands de TLR2 et TLR3 sur des hépatocytes infectés chroniquement par HBV, a montré le plus fort effet antiviral (incluant une médiation… Advisors/Committee Members: Durantel, David (thesis director).

Subjects/Keywords: HBV; Toll-like Récepteurs; Antiviraux; Immunité innée; HBV; Toll-like Receptors; Antivirals; Innate immunity; 572

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Aillot, L. (2018). Effets antiviraux de l'agonisation des Toll-like Récepteurs dans les cellules du foie, une nouvelle stratégie immunothérapeutique dans la lutte contre HBV : Antiviral effects by Toll-like receptors agonisation in liver cells, a new immunotherapeuticstrategy in the fight against HBV. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2018LYSE1139

Chicago Manual of Style (16^th Edition):

Aillot, Ludovic. “Effets antiviraux de l'agonisation des Toll-like Récepteurs dans les cellules du foie, une nouvelle stratégie immunothérapeutique dans la lutte contre HBV : Antiviral effects by Toll-like receptors agonisation in liver cells, a new immunotherapeuticstrategy in the fight against HBV.” 2018. Doctoral Dissertation, Lyon. Accessed April 17, 2021. http://www.theses.fr/2018LYSE1139.

MLA Handbook (7^th Edition):

Aillot, Ludovic. “Effets antiviraux de l'agonisation des Toll-like Récepteurs dans les cellules du foie, une nouvelle stratégie immunothérapeutique dans la lutte contre HBV : Antiviral effects by Toll-like receptors agonisation in liver cells, a new immunotherapeuticstrategy in the fight against HBV.” 2018. Web. 17 Apr 2021.

Vancouver:

Aillot L. Effets antiviraux de l'agonisation des Toll-like Récepteurs dans les cellules du foie, une nouvelle stratégie immunothérapeutique dans la lutte contre HBV : Antiviral effects by Toll-like receptors agonisation in liver cells, a new immunotherapeuticstrategy in the fight against HBV. [Internet] [Doctoral dissertation]. Lyon; 2018. [cited 2021 Apr 17]. Available from: http://www.theses.fr/2018LYSE1139.

Council of Science Editors:

Aillot L. Effets antiviraux de l'agonisation des Toll-like Récepteurs dans les cellules du foie, une nouvelle stratégie immunothérapeutique dans la lutte contre HBV : Antiviral effects by Toll-like receptors agonisation in liver cells, a new immunotherapeuticstrategy in the fight against HBV. [Doctoral Dissertation]. Lyon; 2018. Available from: http://www.theses.fr/2018LYSE1139

21. Foca, Adrien. Identification of PLK1 as a proviral factor for the hepatitis B virus replication : A possible target for antiviral and anticancerous drug development : Développement et utilisation d'ARN interférents dirigés contre PLK1 dans le cadre d'une infection chronique par le virus de l'hépatite B.

Degree: Docteur es, Virologie et cancérologie, 2018, Lyon

URL: http://www.theses.fr/2018LYSE1310

► Dans les régions de fortes endémicités, 70-80% des carcinomes hépatocellulaires sont induits par le VHB. Bien qu’un vaccin prophylactique très efficace existe, il n’est d’aucune… (more)

▼ Dans les régions de fortes endémicités, 70-80% des carcinomes hépatocellulaires sont induits par le VHB. Bien qu’un vaccin prophylactique très efficace existe, il n’est d’aucune utilité pour les 250 millions de personnes chroniquement infectées. Les traitements actuels pour contrôler l'infection chronique par le VHB montrent des limites et le besoin de nouvelles thérapies se fait ressentir. La Polo-like kinase-1 (PLK1), qui joue un rôle essentiel dans la mitose et est surexprimée dans de nombreux cancers, représente une cible prometteuse. Outre son rôle lors de la division cellulaire, PLK1 est impliquée dans la régulation de l'expression des gènes en interphase. Il a été montré que la protéine X du VHB (HBx) active PLK1 dans des modèles de cellules murines. Cependant, il restait à déterminer si PLK1 jouait un rôle au niveau de la réplication du VHB dans des hépatocytes quiescents. Des études récentes ont mis en évidence un lien positif entre l'activation de PLK1 et la réplication du VHB. Le but de ce projet de thèse a été d'étudier le(s) mécanisme(s) par le(s)quel(s) PLK1 jouait un rôle positif sur la réplication virale, avec pour objectif futur d'explorer l’inhibition de PLK1 comme cible antivirale. L'interaction entre PLK1 et la réplication du VHB a d'abord été décrite à l'aide du modèle HepAD38. Dans ce contexte, l'ADN viral est intégré dans le génome hôte, sous le contrôle d'un système d'expression Tet-off. La transcription de l'ARN prégénomique (pgRNA), à la base de la réplication virale, est initiée par la suppression de tétracycline. Dans ce contexte, l'augmentation de l'expression de PLK1 est corrélée avec la régulation négative de deux protéines; SUZ12 et ZNF198, faisant partie de complexes de remodelage de la chromatine. L'inhibition de PLK1 bloque la réplication du VHB, en agissant au niveau de la transcription virale. D'autre part, dans les modèles de réplication du VHB qui miment au mieux une infection, comprenant les hépatocytes primaires humains (PHH) et les cellules non transformées/différenciées HepaRG (dHepaRG), où le VHB se réplique dans des cellules quiescentes, nous avons mis en évidence que: 1) L'inhibition pharmacologique de PLK1 bloque la réplication virale, semblablement en perturbant l’encapsidation du pgRNA via une interaction avec la protéine core du VHB (HBc). 2) Un knocking-down de PLK1 en utilisant des ARN interférents délivrés par nanoparticules lipidiques résulte en une forte baisse de la production de pgRNA et dans la sécrétion des antigènes HBeAg/HBsAg, sans impact sur la viabilité cellulaire. Ce projet a donc permis la preuve de concept que PLK1 pouvait être une cible thérapeutique afin de controler la réplication du VHB. De plus, grâce à la technologie de délivrance par nanoparticules lipidiques d’ARN interférents, nous avons pu cibler spécifiquement les hépatocytes, augmentant de ce fait la spécificité et l’efficacité de nos traitements. Un travail sur la compréhension précise des méchanismes cellulaires impliqués permettra de mieux cerner cette interaction hôte/virus afin de… Advisors/Committee Members: Durantel, David (thesis director).

Subjects/Keywords: PLK1; ARN interférents; Hépatite B; Carcinome hépatocellulaire; Antiviraux; PLK1; SiRNA; HBV; HCC; Antivirals HTA; 570

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Foca, A. (2018). Identification of PLK1 as a proviral factor for the hepatitis B virus replication : A possible target for antiviral and anticancerous drug development : Développement et utilisation d'ARN interférents dirigés contre PLK1 dans le cadre d'une infection chronique par le virus de l'hépatite B. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2018LYSE1310

Chicago Manual of Style (16^th Edition):

Foca, Adrien. “Identification of PLK1 as a proviral factor for the hepatitis B virus replication : A possible target for antiviral and anticancerous drug development : Développement et utilisation d'ARN interférents dirigés contre PLK1 dans le cadre d'une infection chronique par le virus de l'hépatite B.” 2018. Doctoral Dissertation, Lyon. Accessed April 17, 2021. http://www.theses.fr/2018LYSE1310.

MLA Handbook (7^th Edition):

Foca, Adrien. “Identification of PLK1 as a proviral factor for the hepatitis B virus replication : A possible target for antiviral and anticancerous drug development : Développement et utilisation d'ARN interférents dirigés contre PLK1 dans le cadre d'une infection chronique par le virus de l'hépatite B.” 2018. Web. 17 Apr 2021.

Vancouver:

Foca A. Identification of PLK1 as a proviral factor for the hepatitis B virus replication : A possible target for antiviral and anticancerous drug development : Développement et utilisation d'ARN interférents dirigés contre PLK1 dans le cadre d'une infection chronique par le virus de l'hépatite B. [Internet] [Doctoral dissertation]. Lyon; 2018. [cited 2021 Apr 17]. Available from: http://www.theses.fr/2018LYSE1310.

Council of Science Editors:

Foca A. Identification of PLK1 as a proviral factor for the hepatitis B virus replication : A possible target for antiviral and anticancerous drug development : Développement et utilisation d'ARN interférents dirigés contre PLK1 dans le cadre d'une infection chronique par le virus de l'hépatite B. [Doctoral Dissertation]. Lyon; 2018. Available from: http://www.theses.fr/2018LYSE1310

22. Richard, Mathilde. Diversité des mécanismes de résistance aux inhibiteurs de la neuraminidase des virus influenza A : implications de résidus conservés dans le site actif de la neuraminidase et de la balance fonctionnelle entre la neuraminidase et l’hémagglutinine : Diversity of resistance mechanisms to influenza A neuraminidase inhibitors : implication of conserved residues in the neuraminidase active site and of the functional balance between the neuraminidase and the hemagglutinin.

Degree: Docteur es, Virologie, 2010, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2010LYO10323

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Chaque année, les épidémies de grippe, dont les principaux agents étiologiques sont les virus influenza de type A, ont un impact considérable sur la population… (more)

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Chaque année, les épidémies de grippe, dont les principaux agents étiologiques sont les virus influenza de type A, ont un impact considérable sur la population en terme de morbidité et de mortalité. Le virus influenza A comporte à sa surface deux glycoprotéines, la neuraminidase et l’hémagglutinine. Ces deux protéines ont des fonctions antagonistes : l’hémagglutinine permet l’entrée du virus dans la cellule hôte et la neuraminidase, par son activité sialidase, libère les nouveaux virions formés. Bien que la prophylaxie du virus grippal repose essentiellement sur la vaccination, les antiviraux jouent un rôle important dans la lutte contre les épidémies de grippe et dans la stratégie développée en prévision d'une pandémie grippale. Les inhibiteurs de la neuraminidase (INAs) sont des antiviraux efficaces contre la grippe. Ils inhibent l’activité enzymatique de la neuraminidase et empêchent la libération des nouveaux virions formés. La démarche méthodologique qui a conduit à l’élaboration de molécules ciblant la neuraminidase laissait espérer une apparition limitée de résistance. Cependant, des cas de résistances aux INAs ont été mis en évidence lors d’études cliniques. Outre la nécessité d’une surveillance étroite, il est donc important d’étudier et de comprendre les diverses mécanismes susceptibles d’induire une résistance aux INAs. Le travail de cette thèse s’est ainsi porté sur la compréhension de la diversité des mécanismes de résistance. Dans un premier temps, nous avons étudié l’impact de mutations sur l’ensemble des résidus structuraux du site actif de la neuraminidase. Nous avons observé que la plupart de ces mutations n’altéraient pas les caractéristiques du virus et induisaient une légère baisse de sensibilité aux INAs. Par la suite, nous avons cherché à explorer les possibilités de synergie dans la résistance aux INAs par la combinaison de deux mutations structurales du site actif de la neuraminidase. Sur quatre virus produits, seul le virus possédant la double mutation E119V+I222L était viable, malgré une capacité réplicative in vitro altérée. La combinaison de ces deux mutations induit une synergie dans la résistance à l’oseltamivir. Enfin, nous avons voulu intégrer l’interaction fonctionnelle de la neuraminidase avec l’hémagglutinine. Nous avons montré que la combinaison d’une hémagglutinine de faible affinité pour les récepteurs sialylés permettait de restaurer un virus possédant une neuraminidase déficiente. Ainsi, un virus influenza peut se libérer de la fonction de la neuraminidase, cible des seuls antiviraux efficaces disponibles à l’heure actuelle. Les mécanismes de résistances aux inhibiteurs de la neuraminidase sont multiples. L’émergence durant les deux dernières saisons hivernales de virus résistants aux INAs sans pression de sélection a remis en question les hypothèses développées sur l’infectivité et la transmissibilité de souches résistantes, ouvrant de nouvelles perspectives quant à l’étude des mécanismes permettant l’obtention de virus épidémiogènes résistants aux INAs

Each winter,…

Advisors/Committee Members: Lina, Bruno (thesis director).

Subjects/Keywords: Influenza; Neuraminidase; Antiviraux; Résistance; Balance fonctionnelle; Influenza; Neuraminidase; Antivirals; Resistance; Functionnal balance; 616.203

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Richard, M. (2010). Diversité des mécanismes de résistance aux inhibiteurs de la neuraminidase des virus influenza A : implications de résidus conservés dans le site actif de la neuraminidase et de la balance fonctionnelle entre la neuraminidase et l’hémagglutinine : Diversity of resistance mechanisms to influenza A neuraminidase inhibitors : implication of conserved residues in the neuraminidase active site and of the functional balance between the neuraminidase and the hemagglutinin. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2010LYO10323

Chicago Manual of Style (16^th Edition):

Richard, Mathilde. “Diversité des mécanismes de résistance aux inhibiteurs de la neuraminidase des virus influenza A : implications de résidus conservés dans le site actif de la neuraminidase et de la balance fonctionnelle entre la neuraminidase et l’hémagglutinine : Diversity of resistance mechanisms to influenza A neuraminidase inhibitors : implication of conserved residues in the neuraminidase active site and of the functional balance between the neuraminidase and the hemagglutinin.” 2010. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed April 17, 2021. http://www.theses.fr/2010LYO10323.

MLA Handbook (7^th Edition):

Richard, Mathilde. “Diversité des mécanismes de résistance aux inhibiteurs de la neuraminidase des virus influenza A : implications de résidus conservés dans le site actif de la neuraminidase et de la balance fonctionnelle entre la neuraminidase et l’hémagglutinine : Diversity of resistance mechanisms to influenza A neuraminidase inhibitors : implication of conserved residues in the neuraminidase active site and of the functional balance between the neuraminidase and the hemagglutinin.” 2010. Web. 17 Apr 2021.

Vancouver:

Richard M. Diversité des mécanismes de résistance aux inhibiteurs de la neuraminidase des virus influenza A : implications de résidus conservés dans le site actif de la neuraminidase et de la balance fonctionnelle entre la neuraminidase et l’hémagglutinine : Diversity of resistance mechanisms to influenza A neuraminidase inhibitors : implication of conserved residues in the neuraminidase active site and of the functional balance between the neuraminidase and the hemagglutinin. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2010. [cited 2021 Apr 17]. Available from: http://www.theses.fr/2010LYO10323.

Council of Science Editors:

Richard M. Diversité des mécanismes de résistance aux inhibiteurs de la neuraminidase des virus influenza A : implications de résidus conservés dans le site actif de la neuraminidase et de la balance fonctionnelle entre la neuraminidase et l’hémagglutinine : Diversity of resistance mechanisms to influenza A neuraminidase inhibitors : implication of conserved residues in the neuraminidase active site and of the functional balance between the neuraminidase and the hemagglutinin. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2010. Available from: http://www.theses.fr/2010LYO10323

Boston University

23. Buczek, Magdalena Marta. Qualitative study of a primary care-based hepatitis C treatment program at a safety-net hospital.

Degree: MS, Medical Sciences, 2017, Boston University

URL: http://hdl.handle.net/2144/23754

► INTRODUCTION: Mortality associated with hepatitis C virus (HCV) infection is increasing, yet only a small percentage of HCV-infected individuals are aware of their infections, complete… (more)

▼ INTRODUCTION: Mortality associated with hepatitis C virus (HCV) infection is increasing, yet only a small percentage of HCV-infected individuals are aware of their infections, complete treatment, and achieve a cure, defined as a sustained virologic response. In March 2015, the Section of General Internal Medicine at Boston Medical Center (BMC), New England’s largest safety-net hospital, implemented the Adult Primary Care HCV Treatment and Triage Program to increase access to treatment. We are unaware of prior studies that have explored a pharmacist-centered primary care-based HCV treatment model in the era of newer direct-acting antiviral (DAA) medications. OBJECTIVES: To gain a deeper understanding of the roles of each program staff member, as well as an understanding of how primary care providers (PCPs) who refer patients to the program perceive and interact with the program. Such an understanding will help promote implementation and dissemination of the program. METHODS: We conducted in-depth semi-structured interviews with six staff members and with five PCPs in the Section of General Internal Medicine at BMC who refer patients to the program. We asked staff members about their roles and their perception of the program’s impact on patient linkage to HCV treatment. We probed PCPs about their experiences with HCV screening, referral, and follow-up processes, and differences in accessing HCV treatment for their patients prior to and following the implementation of the program. We audiotaped and transcribed interviews, and identified major themes through qualitative analysis. RESULTS: We identified five major themes that characterize how the HCV treatment program delivers care: 1) efficiency (“So here I feel like…they get evaluated…they get treated. Boom, it’s done”); 2) clear and open communication (“…one of the strengths of our program is that we have…a lot of direct contact with patients…”); 3) personalized medicine (“…I've set up the pill box for them [patients]…we tailor it to whatever they need”); 4) high patient engagement (“So if I get a referral for a patient…I call the patient three times. If I haven’t heard from the patient…I send them a letter and I tell the PCP”); 5) patient empowerment through education (“I think patient education is the best thing…if the patient is involved then… they’ll do what they need to do”). Additionally, the public health social worker and the pharmacist play key roles in the program. The social worker supports patients throughout treatment and addresses psychosocial barriers to treatment engagement (“I had a patient…who stopped taking his medication because his apartment was infested with bed bugs…[Social worker] got the patient furniture for free and got an exterminator…”). The pharmacist provides medication management during face-to-face patient visits (“…I go over everything imaginable...proper adherence…adverse effects, interactions…”). CONCLUSIONS: The HCV treatment program at BMC is a promising model to deliver HCV treatment to urban, underserved…

Subjects/Keywords: Medicine; Direct-acting antivirals; Hepatitis C virus; Multidisciplinary team; Pharmacy; Primary care; Social work

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APA (6^th Edition):

Buczek, M. M. (2017). Qualitative study of a primary care-based hepatitis C treatment program at a safety-net hospital. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/23754

Chicago Manual of Style (16^th Edition):

Buczek, Magdalena Marta. “Qualitative study of a primary care-based hepatitis C treatment program at a safety-net hospital.” 2017. Masters Thesis, Boston University. Accessed April 17, 2021. http://hdl.handle.net/2144/23754.

MLA Handbook (7^th Edition):

Buczek, Magdalena Marta. “Qualitative study of a primary care-based hepatitis C treatment program at a safety-net hospital.” 2017. Web. 17 Apr 2021.

Vancouver:

Buczek MM. Qualitative study of a primary care-based hepatitis C treatment program at a safety-net hospital. [Internet] [Masters thesis]. Boston University; 2017. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/2144/23754.

Council of Science Editors:

Buczek MM. Qualitative study of a primary care-based hepatitis C treatment program at a safety-net hospital. [Masters Thesis]. Boston University; 2017. Available from: http://hdl.handle.net/2144/23754

University of California – San Francisco

24. Asher, Alice Kathleen. Hepatitis C virus treatment, people who inject drugs, and treatment barriers in the age of direct-acting antivirals.

Degree: Nursing, 2015, University of California – San Francisco

URL: http://www.escholarship.org/uc/item/1cz9c2f6

► Hepatitis C virus (HCV) infection affects millions of Americans at a high public health cost. Despite the availability of a curative treatment, a significant proportion… (more)

Subjects/Keywords: Nursing; clinicians; direct-acting antivirals; Hepatitis C treatment; People who inject drugs

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APA (6^th Edition):

Asher, A. K. (2015). Hepatitis C virus treatment, people who inject drugs, and treatment barriers in the age of direct-acting antivirals. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/1cz9c2f6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Asher, Alice Kathleen. “Hepatitis C virus treatment, people who inject drugs, and treatment barriers in the age of direct-acting antivirals.” 2015. Thesis, University of California – San Francisco. Accessed April 17, 2021. http://www.escholarship.org/uc/item/1cz9c2f6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Asher, Alice Kathleen. “Hepatitis C virus treatment, people who inject drugs, and treatment barriers in the age of direct-acting antivirals.” 2015. Web. 17 Apr 2021.

Vancouver:

Asher AK. Hepatitis C virus treatment, people who inject drugs, and treatment barriers in the age of direct-acting antivirals. [Internet] [Thesis]. University of California – San Francisco; 2015. [cited 2021 Apr 17]. Available from: http://www.escholarship.org/uc/item/1cz9c2f6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Asher AK. Hepatitis C virus treatment, people who inject drugs, and treatment barriers in the age of direct-acting antivirals. [Thesis]. University of California – San Francisco; 2015. Available from: http://www.escholarship.org/uc/item/1cz9c2f6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

25. Casey, Julia. Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection.

Degree: 2020, University of Toronto

URL: http://hdl.handle.net/1807/103341

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Worldwide, 71 million people are chronically infected with Hepatitis C Virus (HCV). Chronic HCV infection leads to potentially fatal outcomes including liver cirrhosis and hepatocellular… (more)

Subjects/Keywords: Direct Acting Antivirals; Hepatitis C Virus; Immune Exhaustion; Immune Restoration; Protective Immunity; Reinfection; 0982

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Casey, J. (2020). Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/103341

Chicago Manual of Style (16^th Edition):

Casey, Julia. “Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection.” 2020. Masters Thesis, University of Toronto. Accessed April 17, 2021. http://hdl.handle.net/1807/103341.

MLA Handbook (7^th Edition):

Casey, Julia. “Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection.” 2020. Web. 17 Apr 2021.

Vancouver:

Casey J. Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection. [Internet] [Masters thesis]. University of Toronto; 2020. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/1807/103341.

Council of Science Editors:

Casey J. Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection. [Masters Thesis]. University of Toronto; 2020. Available from: http://hdl.handle.net/1807/103341

University of Edinburgh

26. Imhof, Ingrid. Development of an intra- and intergenotypic HCV cell culture method to phenotype and assess antiviral susceptibilities and resistance development of HCV NS3 protease genes from HCV genotypes 1-6.

Degree: PhD, 2010, University of Edinburgh

URL: http://hdl.handle.net/1842/6207

► The development of specific antiviral drugs directly targeting the hepatitis C virus (HCV) is clinically important, as the current standard interferon/ribavirin combination treatment is only… (more)

▼ The development of specific antiviral drugs directly targeting the hepatitis C virus (HCV) is clinically important, as the current standard interferon/ribavirin combination treatment is only partially effective, expensive and often associated with severe side effects. Inhibitors of the NS3 protease (PI) therefore represent a promising alternative or additional therapy. To date, the development and in vitro evaluation of PIs is restricted to the genotype 1/2 based replicon and the genotype 2a full length viral cell culture system. However, proteases of the different HCV genotypes vary substantially in their amino acid sequence and secondary structure and require separate evaluation of their efficacy before they go into clinical trials. To address this issue, a panel of intra- and intergenotypic recombinants based on the recombinant infectious clone Jc1 (pFK JFH1/J6/C-846) was developed in this work. The viability of these recombinants was assessed in the Huh7.5 cell culture system, where replicating viruses were detected by HCV-NS5A immunostaining. Intergenotypic recombinants containing genotype 1a, 1b, 3a, 4a and 6a derived proteases were replication defective, whereas the recombinant with genotype 5a derived protease replicated efficiently after acquiring cell culture adaptive mutations. The replacement of not only the NS3 protease gene region, but also its cofactor NS4A, allowed the generation of replication competent intra- and intergenotypic recombinants for all 6 major genotypes. Replacing the NS3 protease of the recombinants with that of patientderived proteases also generated replicating recombinants, greatly expanding the panel of intergenotypic recombinants available for phenotyping and PI evaluation. However, intra- and intergenotypic recombinants showed substantial differences in their replication kinetics, which may be influenced by naturally occurring polymorphism between genotypes and the differential requirement of adaptive/attenuating cell culture mutations. Genotype 1a recombinants replicated very poorly, which may be due to incompatibilities between the type 1a NS3/4A protease and the type 2a backbone. 50% inhibitory concentrations (IC50) of different PIs were measured using Foci Forming Units/ml (FFU/ml) reductions and replication inhibition assays. The different recombinants showed consistent, genotype-associated differences in their susceptibility to the PI BILN 2061, with genotypes 2a, 3a and 5a derived recombinants showing approximately 100-fold lower susceptibility than genotype 1b, 4a and 6a derived recombinants. These observations are consistent with major differences in response rates found in recent treatment trials of genotype 1, 2 and 3 infected patients. Differences in susceptibility were also observed for VX-950, with genotype 1b, 2a and 6a derived recombinants being twice as susceptible than genotype 3a, 4a and 5a derived recombinants. Passaging the intra- and intergenotypic recombinants under increasing concentrations of PI allowed the identification of PI resistance mutations.…

Subjects/Keywords: 615; HCV; hepatitis C virus; antivirals

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Imhof, I. (2010). Development of an intra- and intergenotypic HCV cell culture method to phenotype and assess antiviral susceptibilities and resistance development of HCV NS3 protease genes from HCV genotypes 1-6. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/6207

Chicago Manual of Style (16^th Edition):

Imhof, Ingrid. “Development of an intra- and intergenotypic HCV cell culture method to phenotype and assess antiviral susceptibilities and resistance development of HCV NS3 protease genes from HCV genotypes 1-6.” 2010. Doctoral Dissertation, University of Edinburgh. Accessed April 17, 2021. http://hdl.handle.net/1842/6207.

MLA Handbook (7^th Edition):

Imhof, Ingrid. “Development of an intra- and intergenotypic HCV cell culture method to phenotype and assess antiviral susceptibilities and resistance development of HCV NS3 protease genes from HCV genotypes 1-6.” 2010. Web. 17 Apr 2021.

Vancouver:

Imhof I. Development of an intra- and intergenotypic HCV cell culture method to phenotype and assess antiviral susceptibilities and resistance development of HCV NS3 protease genes from HCV genotypes 1-6. [Internet] [Doctoral dissertation]. University of Edinburgh; 2010. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/1842/6207.

Council of Science Editors:

Imhof I. Development of an intra- and intergenotypic HCV cell culture method to phenotype and assess antiviral susceptibilities and resistance development of HCV NS3 protease genes from HCV genotypes 1-6. [Doctoral Dissertation]. University of Edinburgh; 2010. Available from: http://hdl.handle.net/1842/6207

The Ohio State University

27. Meister, Gabriel T. Antiviral mechanism(s) of the experimental immunosuppressive agent leflunomide against human cytomegalovirus and polyomavirus.

Degree: PhD, Pathology, 2005, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1111428519

► Leflunomide is an experimental immunosuppressive agent that has shown efficacy as an antiviral agent against human cytomegalovirus (HCMV) and polyomavirus strain BK (BKV). An antiviral… (more)

▼ Leflunomide is an experimental immunosuppressive agent that has shown efficacy as an antiviral agent against human cytomegalovirus (HCMV) and polyomavirus strain BK (BKV). An antiviral regimen has been approved for immunosuppressed patients suffering complications from HCMV infection, whereas a good treatment option for patients infected with BKV does not exist. Unfortunately, the antiviral treatment options for patients infected with HCMV have helped promote the propagation of multi-drug resistant HCMV strains. This body of work illustrates the possible antiviral mechanisms associated with Leflunomide using an in vitro model system. We have tested the hypothesis that the antiviral activity of A77 1726, the active metabolite of Leflunomide, is a result of its inhibition of phosphorylation of one or more viral structural proteins. Western blot, Southern (Dot Blot) blot, and CMV gene array analysis demonstrated that Leflunomide does not inhibit HCMV DNA synthesis, the translation of essential viral proteins, or the transcription of viral mRNA. 32P-orthophosphate labeling experiments confirm a reduction in the phosphorylation of more than one of the HCMV tegument proteins. In addition, immunohistochemical staining showed discrete changes in localization of these tegument proteins in Leflunomide-treated cells. Co-immunoprecipitation experiments confirm that Leflunomide disrupts the interaction of viral tegument proteins suggesting that Leflunomide may inhibit complete infectious virion assembly by altering the phosphorylation states of one or more viral structural proteins. The second aspect of this work was to determine if Leflunomide would inhibit the replication of BKV, a polyoma virus unrelated to HCMV. We tested the hypothesis that A77 1726 would inhibit the production of infectious BKV particles without inhibiting DNA synthesis or large T antigen translation. Plaque assay data demonstrated a log decrease in viral titers when infected cells were treated with A77 1726. Western blot and Southern blot data confirmed the inhibition was not due to a block in protein translation of the large T antigen or a viral DNA synthesis. Immunohistochemistry confirmed there was no reduction of the large T antigen protein when infected cells were treated with A77 1726. When the phosphorylation of the large T antigen was assessed, no reductions in phosphorylation could be detected. Advisors/Committee Members: Waldman, W. (Advisor).

Subjects/Keywords: HCMV; cytomegalovirus; polyomavirus; antivirals; viral replication

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Meister, G. T. (2005). Antiviral mechanism(s) of the experimental immunosuppressive agent leflunomide against human cytomegalovirus and polyomavirus. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1111428519

Chicago Manual of Style (16^th Edition):

Meister, Gabriel T. “Antiviral mechanism(s) of the experimental immunosuppressive agent leflunomide against human cytomegalovirus and polyomavirus.” 2005. Doctoral Dissertation, The Ohio State University. Accessed April 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111428519.

MLA Handbook (7^th Edition):

Meister, Gabriel T. “Antiviral mechanism(s) of the experimental immunosuppressive agent leflunomide against human cytomegalovirus and polyomavirus.” 2005. Web. 17 Apr 2021.

Vancouver:

Meister GT. Antiviral mechanism(s) of the experimental immunosuppressive agent leflunomide against human cytomegalovirus and polyomavirus. [Internet] [Doctoral dissertation]. The Ohio State University; 2005. [cited 2021 Apr 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1111428519.

Council of Science Editors:

Meister GT. Antiviral mechanism(s) of the experimental immunosuppressive agent leflunomide against human cytomegalovirus and polyomavirus. [Doctoral Dissertation]. The Ohio State University; 2005. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1111428519

28. Shimizu, Jacqueline Farinha [UNESP]. Atividade antiviral de compostos naturais no ciclo replicativo do HCV.

Degree: 2016, Universidade Estadual Paulista (UNESP)

URL: http://hdl.handle.net/11449/136314

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A Hepatite C é uma doença causada pelo vírus da Hepatite C (HCV), que afeta milhares de pessoas em todo o mundo. Representa um problema de saúde pública, sendo uma das principais causas de doenças e transplantes relacionados ao fígado. Não há uma vacina contra o HCV e os tratamentos atuais não são eficazes para todos os pacientes tratados, apresentando muitos efeitos colaterais e alto custo de desenvolvimento. Desta forma, fica evidente a necessidade do desenvolvimento de novas abordagens terapêuticas que produzam uma melhor resposta virológica sustentada, efeitos colaterais mais brandos e menor custo de produção. Neste contexto, compostos naturais podem fornecer uma fonte alternativa para a identificação de produtos com potencial terapêutico. O presente trabalho teve como objetivo avaliar os efeitos de compostos naturais, isolados do veneno da serpente Crotalus durissus terrificus (complexo heterodimérico crotoxina e suas subunidades crotapotina e Fosfolipase A2), e do extrato das folhas de Pterogyne nitens (sorbifolina e pedalitina), no ciclo replicativo do HCV in vitro. Estes compostos foram testados quanto às suas atividades antivirais por meio de infecção e tratamento de células Huh-7.5, e realização de ensaios de luciferase, western-blotting e imunofluorescência. Os dados obtidos demonstraram que tanto os compostos isolados de C. durissus terrificus quanto de P. nitens possuem efeito anti-HCV, sendo que alguns compostos inibiram mais de uma etapa do ciclo replicativo viral. Portanto, os múltiplos efeitos anti-HCV apresentados pelo tratamento com esses compostos demonstraram o potencial terapêutico de fontes naturais no tratamento da Hepatite C.

Hepatitis C is a disease caused by Hepatitis C virus (HCV) that affects thousands of people worldwide. Represents a public health problem, being one of the main causes of liver disease and transplantation. There is no vaccine for HCV and the current therapy is not effective for all treated patients, presents many side effects and high cost of development. Thus, there is an evident need to develop new therapeutic approaches which result in a better sustained virologic response, milder side effects and lower production cost. In this context, natural compounds can provide an alternative source for the identification…

Advisors/Committee Members: Universidade Estadual Paulista (UNESP), Jardim, Ana Carolina Gomes [UNESP].

Subjects/Keywords: Vírus da Hepatite C; Antivirais; Compostos naturais; Hepatitis C Virus; Antivirals; Natural compounds

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shimizu, J. F. [. (2016). Atividade antiviral de compostos naturais no ciclo replicativo do HCV. (Masters Thesis). Universidade Estadual Paulista (UNESP). Retrieved from http://hdl.handle.net/11449/136314

Chicago Manual of Style (16^th Edition):

Shimizu, Jacqueline Farinha [UNESP]. “Atividade antiviral de compostos naturais no ciclo replicativo do HCV.” 2016. Masters Thesis, Universidade Estadual Paulista (UNESP). Accessed April 17, 2021. http://hdl.handle.net/11449/136314.

MLA Handbook (7^th Edition):

Shimizu, Jacqueline Farinha [UNESP]. “Atividade antiviral de compostos naturais no ciclo replicativo do HCV.” 2016. Web. 17 Apr 2021.

Vancouver:

Shimizu JF[. Atividade antiviral de compostos naturais no ciclo replicativo do HCV. [Internet] [Masters thesis]. Universidade Estadual Paulista (UNESP); 2016. [cited 2021 Apr 17]. Available from: http://hdl.handle.net/11449/136314.

Council of Science Editors:

Shimizu JF[. Atividade antiviral de compostos naturais no ciclo replicativo do HCV. [Masters Thesis]. Universidade Estadual Paulista (UNESP); 2016. Available from: http://hdl.handle.net/11449/136314

Universidade Nova

29. Brandão, Ruben Alexandre Ribeiro. Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 HCV infected patients in a Portuguese cohort.

Degree: 2018, Universidade Nova

URL: https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/37051

► Hepatitis C virus (HCV) is considered to be the leading cause of hepatocellular carcinoma (HCC). During the last years, several highly efficacy regimens of direct-acting… (more)

▼ Hepatitis C virus (HCV) is considered to be the leading cause of hepatocellular carcinoma (HCC). During the last years, several highly efficacy regimens of direct-acting antivirals (DAAs) with excellent rates of success became available. However, therapeutic failure may occur in up to 10% of treated individuals. Our aim was to study the profile of NS5 coding region RASs in DAA-naive genotype 1 HCV infected patients, as well as to ascertain an association between treatment failure and the presence of baseline NS5 RASs. A comparison between LiPA and Sanger sequencing genotyping methods was also assessed. Plasma RNA from 81 DAA-naïve GT1 HCV infected patients was extracted, followed by an in-house nested RT-PCR of the NS5 coding region. PCR products were purified, leading to Sanger population sequencing on the 3130xl ABI Genetic Analyzer. Sequences were aligned using ChromasPro v1.7.6, and analyzed online in hcv.geno2pheno.org. NS5A RASs were present in 28,4% (23/81) of all GT1 infected patients. The most commonly detected NS5A RAS was Y93C/H with a prevalence of 9,9% (8/81) in all GT1 infected patients. NS5B RASs showed a prevalence of 14,8% (12/81) in all GT1 infected patients, and were only detected in GT1b, being mainly represented by C316N accounting for 40% (10/25). The combined Q30H+Y93H NS5A RASs, were detected at baseline in one HIV/HCV GT1a co-infected patient who later failed a treatment with sofosbuvir/ledipasvir (SOF/LDV) for 12 weeks. An isolated Y93H mutation was also detected at baseline in a relapsing GT1b mono-infected patient. Overall 38,3% (31/81) of all GT1 HCV infected patients presented NS5 RASs at baseline, in which 58% (18/31) were co-infected with HIV/HCV. The obtained data supports the usefulness of resistance testing prior to treatment initiation, as a statistical significant association was found between treatment failure and the baseline presence of specific NS5 RASs, namely Y93C/H (p = 0.04). Advisors/Committee Members: Gomes, Perpétua, Paixão, Paulo.

Subjects/Keywords: Hepatitis C virus; Direct-acting antivirals; Resistance-associated substitutions; NS5A; NS5B; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Brandão, R. A. R. (2018). Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 HCV infected patients in a Portuguese cohort. (Thesis). Universidade Nova. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/37051

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Brandão, Ruben Alexandre Ribeiro. “Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 HCV infected patients in a Portuguese cohort.” 2018. Thesis, Universidade Nova. Accessed April 17, 2021. https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/37051.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Brandão, Ruben Alexandre Ribeiro. “Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 HCV infected patients in a Portuguese cohort.” 2018. Web. 17 Apr 2021.

Vancouver:

Brandão RAR. Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 HCV infected patients in a Portuguese cohort. [Internet] [Thesis]. Universidade Nova; 2018. [cited 2021 Apr 17]. Available from: https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/37051.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Brandão RAR. Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 HCV infected patients in a Portuguese cohort. [Thesis]. Universidade Nova; 2018. Available from: https://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/37051

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Billioud, Gaëtan. Étude des performances de variants du virus de l’hépatite B : Fitness study of hepatitis B virus variants.

Degree: Docteur es, Biologie, 2011, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2011LYO10077

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Les traitements actuels contre le virus de l’hépatite B (VHB) combinent un ou plusieurs analogues de nucléos(t)ides qui inhibent directement la réplication virale en bloquant… (more)

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Les traitements actuels contre le virus de l’hépatite B (VHB) combinent un ou plusieurs analogues de nucléos(t)ides qui inhibent directement la réplication virale en bloquant l’étape de transcription inverse. Ces traitements très efficaces sont pourtant confrontés à l’émergence de virus résistants à ces traitements. Ces résistances sont la conséquence de l’émergence et la sélection de mutants parfois complexes présentant des mutations à la fois dans le gène de la polymérase (pol) et de l’enveloppe virale. Les objectifs principaux de ce doctorat ont été d’étudier la sensibilité des variants résistants du VHB vis-à-vis d’analogues de nucléos(t)ides et de nouveaux composés nonnucléos(t)idiques agissant contre la nucléocapside, mais également de comparer les performances virales de différents mutants afin de comprendre le processus de sélection des mutants qui s’opère chez le patient sous pression thérapeutique. Ces études ont caractérisé la sensibilité de certaines mutations de résistance aux analogues de nucléos(t)ides, de souligner l’importance des modifications de l’enveloppe dues aux mutations de résistance dans le processus d’émergence et de sélection des variants dans la quasi-espèce virale et d’identifier de nouvelles molécules antivirales efficaces permettant, en combinaison avec les analogues de nucléos(t)ide, de diminuer fortement les phénomènes de résistance du VHB. Mieux comprendre les phénomènes de résistance, les procédés d’émergence, de sélection et de transmission des mutants du VHB pour élaborer les meilleures stratégies cliniques de combinaisons thérapeutiques peut réduire considérablement le nombre de personnes touchées par ce virus

Current therapies against the hepatitis B virus (HBV) combine one or more nucleoside analogues that directly inhibit viral replication by blocking reverse transcription step. These treatments are very effective, however, faced with the emergence of viruses resistant to these treatments. These resistances are the result of the emergence and selection of mutants with mutations can be complex in both the polymerase gene (pol) and the viral envelope. The main objectives of this PhD was to study the sensitivity of resistant HBV variants vis-à-vis similar nucleos(t)ides and new compounds non-nucleos(t)idic acting against the nucleocapsid, but also compare the performance of different viral mutants to understand the process of selection of mutants that occurs in patients under therapeutic pressure. These studies have characterized the sensitivity of some resistance mutations to nucleoside analogues, to highlight the importance of the envelope changes due to resistance mutations in the process of emergence and selection of variants in the quasispecies virus and to identify new effective antiviral drugs may allow, in combination with nucleoside analogues, to greatly reduce the phenomenon of HBV resistance. Better understanding the phenomenon of resistance, the processes of emergence, selection and transmission of HBV mutants to develop the best clinical strategies of combination…

Advisors/Committee Members: Zoulim, Fabien (thesis director).

Subjects/Keywords: VHB; Performances; Antiviraux; Analogues de nucléosides; Résistance; Sélection; Quasi-espèce; HBV; Fitness; Antivirals; Nucleoside analogs; Resistance; Selection; Quasi-species; 616.91

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Billioud, G. (2011). Étude des performances de variants du virus de l’hépatite B : Fitness study of hepatitis B virus variants. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2011LYO10077

Chicago Manual of Style (16^th Edition):

Billioud, Gaëtan. “Étude des performances de variants du virus de l’hépatite B : Fitness study of hepatitis B virus variants.” 2011. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed April 17, 2021. http://www.theses.fr/2011LYO10077.

MLA Handbook (7^th Edition):

Billioud, Gaëtan. “Étude des performances de variants du virus de l’hépatite B : Fitness study of hepatitis B virus variants.” 2011. Web. 17 Apr 2021.

Vancouver:

Billioud G. Étude des performances de variants du virus de l’hépatite B : Fitness study of hepatitis B virus variants. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2011. [cited 2021 Apr 17]. Available from: http://www.theses.fr/2011LYO10077.

Council of Science Editors:

Billioud G. Étude des performances de variants du virus de l’hépatite B : Fitness study of hepatitis B virus variants. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2011. Available from: http://www.theses.fr/2011LYO10077

Open Access Theses and Dissertations