subject:(antiviral)

Penn State University

1. Bhushan, Gitanjali L. Iminosugars with endoplasmic reticulum alpha-glucosidase inhibitor activity are potent inhibitors of Zika virus replication in vitro.

Degree: 2018, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/16052glb5150

► Zika virus (ZIKV) is a vector-borne virus of the family Flaviviridae, which continues to spread and remains a major global public health threat. Currently, there… (more)

▼ Zika virus (ZIKV) is a vector-borne virus of the family Flaviviridae, which continues to spread and remains a major global public health threat. Currently, there are no approved vaccines or antivirals against ZIKV. In this study, the anti-ZIKV ability of four iminosugars with endoplasmic reticulum α- glucosidase inhibitor (ER-AGI) activity namely, deoxynojirimycin (DNJ), N-nonyl deoxynojirimycin (NN-DNJ), castanospermine and celgosivir were investigated. None of the four ER-AGIs showed any significant (p>0.05) cytotoxicity in Vero and human microglia (CHME-3) cells from 0.01 M to 100 M concentrations. Iminosugar treatment of Vero or CHME-3 cells infected with ZIKV at a MOI of 0.5 or 5 resulted in significant inhibition of ZIKV replication and the reduction in ZIKV replication was not associated with any significant change in the expression levels of key antiviral genes. Iminosugars protect cells from ZIKV cytopathogenicity as iminosugar treated Vero and CHME-3 cells showed little or no cell death, whereas vehicle control cells exhibited 50-60% cytopathic effect (CPE) at 72 h following ZIKV infection. We further investigated if CPE was the result of apoptosis and/or necrosis. The difference in apoptosis was measured using an activated caspase 3 and 7 assay, and necrosis was evaluated by using a lactate dehydrogenase (LDH) assay in iminosugar treated and control cells following ZIKV infection at a MOI of 1. There was no difference in apoptosis between iminosugar treated and control cells at 48 and 72 hours post infection (hpi). Unlike iminosugars treated cells, untreated control cells exhibited substantial elevation of necrosis at 72 hpi compared with mock-infected cells. In summary, iminosugars with ER-AGI function inhibit ZIKV replication without altering the antiviral gene expression of human cells. The results of this study strongly suggest that ER-AGIs are promising anti-ZIKV antiviral agents and such warrant further in vivo studies. Advisors/Committee Members: Suresh Varma Kuchipudi, Thesis Advisor/Co-Advisor, Anthony Paul Schmitt, Committee Member, Troy Clavell Sutton, Committee Member, Santhosh Girirajan, Committee Member.

Subjects/Keywords: Zika virus; antiviral

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APA (6^th Edition):

Bhushan, G. L. (2018). Iminosugars with endoplasmic reticulum alpha-glucosidase inhibitor activity are potent inhibitors of Zika virus replication in vitro. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/16052glb5150

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):

Bhushan, Gitanjali L. “Iminosugars with endoplasmic reticulum alpha-glucosidase inhibitor activity are potent inhibitors of Zika virus replication in vitro.” 2018. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/16052glb5150.

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

MLA Handbook (7^th Edition):

Bhushan, Gitanjali L. “Iminosugars with endoplasmic reticulum alpha-glucosidase inhibitor activity are potent inhibitors of Zika virus replication in vitro.” 2018. Web. 13 Apr 2021.

Vancouver:

Bhushan GL. Iminosugars with endoplasmic reticulum alpha-glucosidase inhibitor activity are potent inhibitors of Zika virus replication in vitro. [Internet] [Thesis]. Penn State University; 2018. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/16052glb5150.

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

Council of Science Editors:

Bhushan GL. Iminosugars with endoplasmic reticulum alpha-glucosidase inhibitor activity are potent inhibitors of Zika virus replication in vitro. [Thesis]. Penn State University; 2018. Available from: https://submit-etda.libraries.psu.edu/catalog/16052glb5150

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

University of New South Wales

2. Lim, Kun Lee. A study of norovirus: molecular epidemiology, pathogenesis and antiviral development.

Degree: Biotechnology & Biomolecular Sciences, 2015, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/55031 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:36394/SOURCE02?view=true

► Norovirus (NoV) is one of the most common human pathogens that causes acute gastroenteritis globally. NoVs which belong to a single genotype (of more than… (more)

▼ Norovirus (NoV) is one of the most common human pathogens that causes acute gastroenteritis globally. NoVs which belong to a single genotype (of more than 36) namely the Genogroup II, genotype 4 (GII.4), are of particularly importance because they are responsible for ~70% of all NoV infections globally. The emergence of a novel NoV GII.4 variant occurs every two to three years and leads to an increase in gastroenteritis cases and outbreaks. Hence it is important to continuously monitor the circulation of NoV strains. The first aim of this thesis was to study the molecular epidemiology of NoV in the Asia Pacific region including; Singapore, Australia and New Zealand. In this study, three comprehensive molecular epidemiological studies were performed to characterise NoV strains circulating in Singapore (2004 – 2011), Australia (2010 – 2014) and New Zealand (2013 – 2014). GII.4 viruses were the most predominant NoVs identified in all three regions (54.7 – 80.8%) during the study period. A novel GII.4 pandemic variant, Sydney 2012 was also first identified in early 2012. Generally the temporal dominance of GII.4 variants identified in this study coincided with global pandemics of gastroenteritis. Also, recombination was commonly detected in NoVs from this study cohort which could classify viruses into 21 distinct recombinant types. The mitigation or infection control of NoV is difficult due to the lack of effective vaccine or antiviral. This is partly due to limitations in propagating human NoV in cell culture, which has hampered the study of NoV biology, antiviral development and pathogenesis. Another aim of this thesis was to understand how MNV infection avoids the host innate immune response using murine NoV (MNV) as a surrogate model of human NoV. Work in this thesis provides evidence that NoV employs strategies to regulate type-I IFN signalling pathways by inhibiting IRF3 activation by phosphorylation. This thesis also aimed to use the MNV cell culture model to assess the inhibitory effect of four recently identified non-nucleoside inhibitors. The compounds represent early stage, first-in-class antiviral compounds directly targeting the viral polymerase. Results showed each compound had low micromolar inhibitory activity against NoV in this system. The compounds provide a starting framework for the development of NoV targeted antivirals. Overall this thesis has provided insights into the molecular epidemiology of NoV in Singapore, Australia and New Zealand, host-virus interactions pertaining to the innate immune response and assessed the efficacy of direct-acting antiviral agents against NoV. Advisors/Committee Members: White, Peter A, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW.

Subjects/Keywords: Antiviral; Norovirus; Epidemiology

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APA (6^th Edition):

Lim, K. L. (2015). A study of norovirus: molecular epidemiology, pathogenesis and antiviral development. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/55031 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:36394/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Lim, Kun Lee. “A study of norovirus: molecular epidemiology, pathogenesis and antiviral development.” 2015. Doctoral Dissertation, University of New South Wales. Accessed April 13, 2021. http://handle.unsw.edu.au/1959.4/55031 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:36394/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Lim, Kun Lee. “A study of norovirus: molecular epidemiology, pathogenesis and antiviral development.” 2015. Web. 13 Apr 2021.

Vancouver:

Lim KL. A study of norovirus: molecular epidemiology, pathogenesis and antiviral development. [Internet] [Doctoral dissertation]. University of New South Wales; 2015. [cited 2021 Apr 13]. Available from: http://handle.unsw.edu.au/1959.4/55031 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:36394/SOURCE02?view=true.

Council of Science Editors:

Lim KL. A study of norovirus: molecular epidemiology, pathogenesis and antiviral development. [Doctoral Dissertation]. University of New South Wales; 2015. Available from: http://handle.unsw.edu.au/1959.4/55031 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:36394/SOURCE02?view=true

3. Oliveira, Oneide Facundo Vasconcelos de. Mentol : avaliação da atividade larvicida e antiviral frente ao vírus zika.

Degree: 2019, Universidade de Fortaleza; Mestrado Em Ciências Médicas; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu

URL: https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=112054 ; http://dspace.unifor.br/handle/tede/112054

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Made available in DSpace on 2021-03-20T00:25:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-30

Menthol is a well-known cyclic monoterpenic alcohol of the industry… (more)

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Made available in DSpace on 2021-03-20T00:25:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-30

Menthol is a well-known cyclic monoterpenic alcohol of the industry in general with anesthetic, anti-inflammatory, antiparasitic, antitussive properties and for its peculiar odor and refreshing sensation is widely used by cigarette manufacturers and oral care products. The aim of this research was to evaluate the effect of Menthol in two strands as larvicide on Aedes larvae and as antiviral in C6 / 36 and Vero cells. The Menthol larvicidal test was used at concentrations of (500, 250, 100 and 50 ¿g / mL) and was performed in triplicate. At each dilution 50 mosquito larvae were used in the third instar of the species Aedes aegypti and Aedes albopictus and were determined at LC50 and LC90. Antiviral activity was evaluated in Vero cells (in vitro) at C6 / 36 (in vitro) and, for this, the cytotoxicity of Menthol in these cells was first determined. Therefore, the colorimetric assay by MTT (3- (4,5-dimethylthiazol-2-yl) -5-diphenyltetrazolium bromide) was performed at concentrations of 1000; 500; 250; 125; 62.5; 31.25 ¿g / mL. The CC50 in cells C6 / 36 = 248 ¿g / mL and Vero = 222.7 ¿g / mL. To determine antiviral activity, EC50 and subsequently the selectivity index (IS) were calculated. In addition, tests were performed (pre-treatment, post-treatment and virucidal treatment) at concentrations 125; 62.5 and 31.25 ¿g / mL. The tests were done in triplicate and with the use of viral control and cell control. Larvicidal tests showed that Menthol has larvicidal activity in Aedes aegypti larvae of LC50 = 162.09 ¿g / mL and CL90 = 358.19 ¿g / mL. Menthol demonstrated antiviral activity at post-treatment concentrations tested in C6 / 36 cells with EC50 = 55.71 ¿g / mL and in the Vero cell virucidal test with EC50 = 64.6 ¿g / mL and R2 = 0 , 95. Therefore, in this research we observed a larvicidal action of Menthol against Aedes aegypti mosquito larvae and the antiviral action of Menthol against Zika Virus and on C6 / 36 and Vero cells. Key words: Aedes; Antivirals; Arbovirose; Menthol; Zika vírus.

Mentol é um álcool monoterpênico cíclico muito conhecido da indústria em geral com propriedades anestésicas, anti-inflamatórias, antiparasitárias, antitussígeno e por seu odor peculiar e sensação de refrescância é bastante utilizado pelos produtores de cigarros e em produtos de higiene bucal. O objetivo dessa pesquisa foi avaliar o efeito do Mentol em duas vertentes como larvicida sobre as larvas do Aedes e como antiviral em células C6/36 e Vero. O teste larvicida com Mentol foi utilizado nas concentrações de (500, 250, 100 e 50 ¿g/mL) e foi realizado em triplicata. Em cada diluição foram utilizadas 50 larvas de mosquito no terceiro instar da espécie Aedes aegypti e Aedes albopictus e foi determinado a CL50 e CL90. A atividade antiviral foi avaliada nas células Vero (in vitro) em C6/36 (in vitro) e, para isso, primeiramente foi determinada a citotoxicidade do Mentol nessas células. Portanto isso, foi realizado o ensaio…

Advisors/Committee Members: Lima, Danielle Malta, Lima, Danielle Malta, Barros, Adriana Rolim Campos, Nogueira Sobrinho, Antonio Carlos.

Subjects/Keywords: Zika vírus; Antiviral

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APA (6^th Edition):

Oliveira, O. F. V. d. (2019). Mentol : avaliação da atividade larvicida e antiviral frente ao vírus zika. (Masters Thesis). Universidade de Fortaleza; Mestrado Em Ciências Médicas; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu. Retrieved from https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=112054 ; http://dspace.unifor.br/handle/tede/112054

Chicago Manual of Style (16^th Edition):

Oliveira, Oneide Facundo Vasconcelos de. “Mentol : avaliação da atividade larvicida e antiviral frente ao vírus zika.” 2019. Masters Thesis, Universidade de Fortaleza; Mestrado Em Ciências Médicas; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu. Accessed April 13, 2021. https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=112054 ; http://dspace.unifor.br/handle/tede/112054.

MLA Handbook (7^th Edition):

Oliveira, Oneide Facundo Vasconcelos de. “Mentol : avaliação da atividade larvicida e antiviral frente ao vírus zika.” 2019. Web. 13 Apr 2021.

Vancouver:

Oliveira OFVd. Mentol : avaliação da atividade larvicida e antiviral frente ao vírus zika. [Internet] [Masters thesis]. Universidade de Fortaleza; Mestrado Em Ciências Médicas; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu; 2019. [cited 2021 Apr 13]. Available from: https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=112054 ; http://dspace.unifor.br/handle/tede/112054.

Council of Science Editors:

Oliveira OFVd. Mentol : avaliação da atividade larvicida e antiviral frente ao vírus zika. [Masters Thesis]. Universidade de Fortaleza; Mestrado Em Ciências Médicas; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu; 2019. Available from: https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=112054 ; http://dspace.unifor.br/handle/tede/112054

University of Alberta

4. Marcet, Candy. Antiviral and cytokine responses of human mast cells to influenza A virus infection.

Degree: PhD, Department of Medicine, 2010, University of Alberta

URL: https://era.library.ualberta.ca/files/4t64gn53b

► Mast cells are immune cells important in innate immunity. Besides their role in asthma and allergies, mast cells are critical effector cells against various pathogens.… (more)

▼ Mast cells are immune cells important in innate immunity. Besides their role in asthma and allergies, mast cells are critical effector cells against various pathogens. Mast cells are established to be protective against bacterial infections, but little is known about their functions in viral infections. Mast cells are abundant in the lungs where influenza A virus (FluA) enter the host. We measured mRNA transcription, protein translation, and synthesis of new viral particles in FluA-treated mast cells. While expression of FluA mRNA and proteins followed similar time courses in both mast cells and epithelial cells, mast cells released a near absence of FluA. We also studied mast cell cytokine release in response to FluA and other viral-associated stimuli such as TLR ligands and type I interferons. Mast cells released the cytokines IL-6 and TGF-, and chemokines CXCL8 and CCL5 in response to various viral stimuli. However, different stimuli were capable of inducing release of different mediator subsets, demonstrating the specificity of mast cell responses. Since FluA infection of mast cells produce little new FluA virions, we investigated whether FluA induces expression of antiviral proteins in mast cells. FluA treatment resulted in mast cell expression of antiviral proteins, namely myxovirus resistance protein A, protein kinase R, interferon stimulated gene 15, viral stress inducible protein 56, and endothelial nitric oxide synthase. Next, we performed co-culture experiments using FluA-infected epithelial cells with or without the addition of mast cells. Our results showed that mast cells in co-culture inhibited the expression of the viral hemagglutinin protein in FluA-infected epithelial cells. Also, preliminary results showed that addition of mast cells protected epithelial cells from FluA infection by limiting the release of FluA particles and reducing epithelial cell death. Our discovery that mast cells produce little virus and express antiviral proteins suggest that mast cells have antiviral mechanisms to restrict FluA infection. This concept was further supported by evidence that mast cells are protective against FluA infection in epithelial cells. This research provides a better understanding of mast cells in innate immunity and may reveal unique antiviral mechanisms valuable in the development of antiviral therapeutics.

Subjects/Keywords: cytokine; virus; mast; antiviral; influenza

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

APA (6^th Edition):

Marcet, C. (2010). Antiviral and cytokine responses of human mast cells to influenza A virus infection. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/4t64gn53b

Chicago Manual of Style (16^th Edition):

Marcet, Candy. “Antiviral and cytokine responses of human mast cells to influenza A virus infection.” 2010. Doctoral Dissertation, University of Alberta. Accessed April 13, 2021. https://era.library.ualberta.ca/files/4t64gn53b.

MLA Handbook (7^th Edition):

Marcet, Candy. “Antiviral and cytokine responses of human mast cells to influenza A virus infection.” 2010. Web. 13 Apr 2021.

Vancouver:

Marcet C. Antiviral and cytokine responses of human mast cells to influenza A virus infection. [Internet] [Doctoral dissertation]. University of Alberta; 2010. [cited 2021 Apr 13]. Available from: https://era.library.ualberta.ca/files/4t64gn53b.

Council of Science Editors:

Marcet C. Antiviral and cytokine responses of human mast cells to influenza A virus infection. [Doctoral Dissertation]. University of Alberta; 2010. Available from: https://era.library.ualberta.ca/files/4t64gn53b

5. Nielsen, Alexander J. Novel Wittig and Organocatalytic Methodologies for the Synthesis of Chemotherapeutic Compounds.

Degree: PhD, 2019, McMaster University

URL: http://hdl.handle.net/11375/24463

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This thesis is primarily focused on the development of Wittig methodologies and the applications of the product alkenes in organocatalysis and drug discovery. Herein is… (more)

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This thesis is primarily focused on the development of Wittig methodologies and the applications of the product alkenes in organocatalysis and drug discovery. Herein is described an aqueous Wittig methodology for the synthesis of α-methylstilbenes and their use in the preparation of novel triazole stilbene inhibitors of aromatase, a clinically validated target for the treatment of estrogen receptor positive breast cancer. As well, a one-step, stereoselective synthesis of alkenyl phenols was developed. The method provides easy access to a variety of compounds that contain this synthetically and biologically important functionality, including natural product phenolic stilbenes. In turn, alkenyl phenols were used as a key component in a novel organocatalytic methodology for the synthesis of cyclobutanes in good yields and high enantioselectivity. Notably, this is one of relatively few asymmetric, catalytic methods for cyclobutane synthesis. Preliminary biological activity of some of these cyclobutane derivatives is reported, including promising anti-cancer activity. Finally, a ten-step total synthesis of the Amaryllidaceae alkaloid (+)-trans-dihydronarciclasine was completed. The synthesis features an organocatalytic Michael-aldol cascade on a cinnamaldehyde derivative, which was prepared using a Wittig methodology previous reported by the McNulty group. Importantly, this compound was found to be one of the most potent anti-Zika compounds reported to date. Future work should focus on improving the potency and selectivity of the various aforementioned chemotherapeutics, with concurrent efforts to build upon the novel methodologies discussed herein.

Thesis

Doctor of Philosophy (PhD)

The Wittig reaction is one of the best ways to make alkenes, a type of reactive bond between two carbon atoms. A new Wittig reaction was developed and used in the preparation and discovery of potent inhibitors of aromatase, an enzyme responsible for the proliferation of many breast cancers. As well, another Wittig methodology was created for the straightforward synthesis of an otherwise difficult to prepare class of alkenes. In turn, these types of alkenes were used in a novel preparation of cyclobutanes, a chemical structure that is difficult to make but can impart useful properties to drugs and materials. Finally, a Wittig reaction previously reported by the McNulty group was used as part of a chemical synthesis of trans-dihydronarciclasine, a rare natural product isolated from daffodils. Trans-dihydronarciclasine was discovered to have antiviral activity and is one of the most potent inhibitors of the Zika virus discovered to date.

Advisors/Committee Members: McNulty, James, Chemical Biology.

Subjects/Keywords: Wittig; organocatalysis; chemotherapeutics; anticancer; antiviral

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APA (6^th Edition):

Nielsen, A. J. (2019). Novel Wittig and Organocatalytic Methodologies for the Synthesis of Chemotherapeutic Compounds. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/24463

Chicago Manual of Style (16^th Edition):

Nielsen, Alexander J. “Novel Wittig and Organocatalytic Methodologies for the Synthesis of Chemotherapeutic Compounds.” 2019. Doctoral Dissertation, McMaster University. Accessed April 13, 2021. http://hdl.handle.net/11375/24463.

MLA Handbook (7^th Edition):

Nielsen, Alexander J. “Novel Wittig and Organocatalytic Methodologies for the Synthesis of Chemotherapeutic Compounds.” 2019. Web. 13 Apr 2021.

Vancouver:

Nielsen AJ. Novel Wittig and Organocatalytic Methodologies for the Synthesis of Chemotherapeutic Compounds. [Internet] [Doctoral dissertation]. McMaster University; 2019. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/11375/24463.

Council of Science Editors:

Nielsen AJ. Novel Wittig and Organocatalytic Methodologies for the Synthesis of Chemotherapeutic Compounds. [Doctoral Dissertation]. McMaster University; 2019. Available from: http://hdl.handle.net/11375/24463

University of Cambridge

6. Mears, Harriet Victoria. On the expression, function and regulation of the murine Ifit family of antiviral RNA-binding proteins.

Degree: PhD, 2020, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/300608

► IFIT proteins are highly expressed as part of the cell-intrinsic immune response following viral infection. In humans, IFIT1 inhibits translation at the initiation stage by… (more)

▼ IFIT proteins are highly expressed as part of the cell-intrinsic immune response following viral infection. In humans, IFIT1 inhibits translation at the initiation stage by binding directly to the 5' terminus of foreign RNA, precluding the recruitment of the cap-binding translation initiation factor complex eIF4F. IFIT1 is highly specific for ‘non-self’ cap0 RNA, which lacks methylation on the first and second cap-proximal nucleotides, but at high concentrations may also restrict ‘self’ cap1 translation. Knock-out mouse models have been extensively used to study IFIT antiviral activity and, more recently, vaccines based on the antiviral activity of IFIT1 have been trialled for efficacy in mice. However, it is becoming clear that there are differences in murine and human IFIT function and regulation, which impacts the interpretation of these models. Mice lack a true orthologue of IFIT1 and instead the closely related Ifit1b has been duplicated twice, yielding three paralogues: Ifit1, Ifit1b and Ifit1c. Murine Ifit1, like human IFIT1, can bind to cap0 RNA and inhibit its translation, but lacks cap1 binding activity. Ifit1b and Ifit1c are closely related to Ifit1 and share many of the residues critical for RNA-binding, but their precise functions are unknown. In this thesis, the expression of the entire murine Ifit family was examined in different mouse cell lines, validating expression of Ifit1b and Ifit1c following interferon stimulation. The murine Ifit family was then recombinantly expressed and purified, allowing biochemical characterisation. It was discovered that Ifit1b, a previously uncharacterised protein, preferentially inhibited the translation of cap1 mRNA, while cap0 and cap2 mRNAs were inhibited to a much lesser extent. Specific cap1 binding allows Ifit1b to inhibit a proportion of cellular translation and block translation of murine hepatitis virus, a cap1 coronavirus. However, both Ifit1 and Ifit1b were incapable of inhibiting translation from a more structured Zika virus reporter mRNA. The same reporter was effectively inhibited by human IFIT1, highlighting a key difference between the activities of human and murine IFIT proteins. IFIT proteins are known to form both homo- and hetero-oligomers, but the functional significance of these interactions is unclear. Here, interaction between human IFIT1 and IFIT3 was shown to increase the stability of both proteins and stimulate translation inhibition by IFIT1. IFIT1 and IFIT3 interacted via a C-terminal YxxxL motif, and disruption of this motif in either protein abolished the cofactor activity of IFIT3, both in vitro and in cells. In mice, Ifit3 is truncated and lacks the YxxxL motif, thus precluding interaction with murine Ifit1. However, this motif is maintained in Ifit1, Ifit1b and Ifit1c, which were found to interact with one-another in vitro. Interaction between murine Ifit proteins increased their stability and Ifit1c enhanced translation inhibition by Ifit1 and Ifit1b in vitro, thereby acting analogously to human IFIT3. Together this work…

Subjects/Keywords: Innate immunity; Interferon; Antiviral response

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APA (6^th Edition):

Mears, H. V. (2020). On the expression, function and regulation of the murine Ifit family of antiviral RNA-binding proteins. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/300608

Chicago Manual of Style (16^th Edition):

Mears, Harriet Victoria. “On the expression, function and regulation of the murine Ifit family of antiviral RNA-binding proteins.” 2020. Doctoral Dissertation, University of Cambridge. Accessed April 13, 2021. https://www.repository.cam.ac.uk/handle/1810/300608.

MLA Handbook (7^th Edition):

Mears, Harriet Victoria. “On the expression, function and regulation of the murine Ifit family of antiviral RNA-binding proteins.” 2020. Web. 13 Apr 2021.

Vancouver:

Mears HV. On the expression, function and regulation of the murine Ifit family of antiviral RNA-binding proteins. [Internet] [Doctoral dissertation]. University of Cambridge; 2020. [cited 2021 Apr 13]. Available from: https://www.repository.cam.ac.uk/handle/1810/300608.

Council of Science Editors:

Mears HV. On the expression, function and regulation of the murine Ifit family of antiviral RNA-binding proteins. [Doctoral Dissertation]. University of Cambridge; 2020. Available from: https://www.repository.cam.ac.uk/handle/1810/300608

University of Hawaii – Manoa

7. Co, Juliene Kimberly G. IFN-α and β restrict JC virus replication in primary human fetal glial cells : implications for progressive multifocal leukoencephalopathy therapy.

Degree: MS, 2011, University of Hawaii – Manoa

URL: http://hdl.handle.net/10125/20442

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viii, 69 leaves, bound ill. 29 cm

Among the severely immunocompromised, IC virus ( JCV) may cause a fatal demyelinating disease, progressive multifoca1leukoencephalopathy (PML). Highly… (more)

Subjects/Keywords: Interferon – Therapeutic use; Antiviral agents

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APA (6^th Edition):

Co, J. K. G. (2011). IFN-α and β restrict JC virus replication in primary human fetal glial cells : implications for progressive multifocal leukoencephalopathy therapy. (Masters Thesis). University of Hawaii – Manoa. Retrieved from http://hdl.handle.net/10125/20442

Chicago Manual of Style (16^th Edition):

Co, Juliene Kimberly G. “IFN-α and β restrict JC virus replication in primary human fetal glial cells : implications for progressive multifocal leukoencephalopathy therapy.” 2011. Masters Thesis, University of Hawaii – Manoa. Accessed April 13, 2021. http://hdl.handle.net/10125/20442.

MLA Handbook (7^th Edition):

Co, Juliene Kimberly G. “IFN-α and β restrict JC virus replication in primary human fetal glial cells : implications for progressive multifocal leukoencephalopathy therapy.” 2011. Web. 13 Apr 2021.

Vancouver:

Co JKG. IFN-α and β restrict JC virus replication in primary human fetal glial cells : implications for progressive multifocal leukoencephalopathy therapy. [Internet] [Masters thesis]. University of Hawaii – Manoa; 2011. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10125/20442.

Council of Science Editors:

Co JKG. IFN-α and β restrict JC virus replication in primary human fetal glial cells : implications for progressive multifocal leukoencephalopathy therapy. [Masters Thesis]. University of Hawaii – Manoa; 2011. Available from: http://hdl.handle.net/10125/20442

University of Hawaii – Manoa

8. Yang, Baojun. Cellular response of insect cells to virus infection.

Degree: 2015, University of Hawaii – Manoa

URL: http://hdl.handle.net/10125/100551

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Ph.D. University of Hawaii at Manoa 2014.

RNA interference (RNAi) is the dsRNA-triggered gene regulatory mechanism that is evolutionally conserved in most eukaryotic cells. It… (more)

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Ph.D. University of Hawaii at Manoa 2014.

RNA interference (RNAi) is the dsRNA-triggered gene regulatory mechanism that is evolutionally conserved in most eukaryotic cells. It has been widely used as a powerful tool for functional genomics in various organisms. In flies, mosquitoes or other insect cells, gene functional analysis by RNAi is usually performed through introduced dsRNAs that are synthesized by in vitro transcription. RNAi serves as an important innate immunity against viruses in plants and invertebrates. It has recently been shown that Aedes albopictus mosquito C6/36 cells, commonly used for arbovirus propagation, possess an impaired RNAi pathway. In this study, we developed in vitro Dicer assay using extracts prepared from mosquito cells. Our results confirmed the inability of C6/36 cells to process dsRNAs into siRNAs, which is consistent with the loss-of-function of Dcr-2 due to a frameshift mutation. However, such a defect could not be complemented by introduction of Drosophila Dicer-2. To evaluate the RNAi-based antiviral mechanism in C6/36 cells, we analyzed the replication of a mutant Nodamura virus (NoV) genomic RNA1 of which viral RNAi suppressor B2 is not expressed (NoVR1ΔB2) and cannot accumulate to a detectable level in RNAi-competent cells. In C6/36 cells, the defective RNAi gives rise to complete restoration of NoVR1ΔB2 replication, suggesting that RNAi is the primary antiviral immunity in mosquito cells. At present, dsRNA, as the trigger of the antiviral RNAi pathway in invertebrate and plants, is the major efficiency limitation factor in RNAi. In this study, a plasmid-based system was developed to express dsRNA intracellular from a DNA cassette containing two convergent T7 promoters in Drosophila S2 cells. Efficient knockdown of a transiently expressed reporter gene or an endogenous gene can be achieved by dsRNA expressed from the system. A random cDNA library was constructed in the dsRNA expression cassette and initial screening led to identification of two host factors that are involved in antiviral response in Drosophila S2 cells. The plasmid-based dsRNA expression system provides an alternative tool for functional genomics in Drosophila and other insect cells.

Subjects/Keywords: Antiviral; dsRNA; RNAi; Innate Immunity

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

APA (6^th Edition):

Yang, B. (2015). Cellular response of insect cells to virus infection. (Thesis). University of Hawaii – Manoa. Retrieved from http://hdl.handle.net/10125/100551

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):

Yang, Baojun. “Cellular response of insect cells to virus infection.” 2015. Thesis, University of Hawaii – Manoa. Accessed April 13, 2021. http://hdl.handle.net/10125/100551.

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

MLA Handbook (7^th Edition):

Yang, Baojun. “Cellular response of insect cells to virus infection.” 2015. Web. 13 Apr 2021.

Vancouver:

Yang B. Cellular response of insect cells to virus infection. [Internet] [Thesis]. University of Hawaii – Manoa; 2015. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10125/100551.

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

Council of Science Editors:

Yang B. Cellular response of insect cells to virus infection. [Thesis]. University of Hawaii – Manoa; 2015. Available from: http://hdl.handle.net/10125/100551

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

University of Edinburgh

9. Jasim, Seema Naseralla. The characterisation of a novel family of peptides with potent anti-viral activity against influenza viruses.

Degree: PhD, 2016, University of Edinburgh

URL: http://hdl.handle.net/1842/25396

► Avian influenza viruses can cause devastating outbreaks in domesticated poultry, with rapid transmission of virus between birds and high mortality. Current measures for control of… (more)

▼ Avian influenza viruses can cause devastating outbreaks in domesticated poultry, with rapid transmission of virus between birds and high mortality. Current measures for control of influenza involve surveillance, closure of live poultry markets and mass culling. However, despite implementing these measures, outbreaks continue. Considering the uncertainty over whether certain strains of avian influenza viruses will adapt to human transmission and limitations over how their spread may be controlled, this study considers the use of anti-viral peptides as protective agents against low pathogenicity avian influenza (LPAI) virus. This study investigated the activity and mode of action of two cell-penetrating anti-viral peptide families against influenza A virus infection: ‘FluPep’ (a family of short, hydrophobic peptides related to suppressor of cytokine signaling- 1 proteins) and ‘Entry Blocker’ (derived from the signal sequence of fibroblast growth factor-4). Plaque reduction assays demonstrated dose-dependent anti-viral activity of both peptide families against a panel of influenza viruses with diverse haemagglutinin subtypes. Determination of IC50 values showed strain-specific differences in sensitivity to FluPep but not Entry Blocker. The IC50 of FluPep 4 for A/PR/8/34 was reduced by reassorting in the HA and NA from a relatively sensitive avian strain using a reverse genetics approach, suggesting inhibitory effects on the viral glycoproteins. Accordingly, viral entry assays focusing on binding, internalisation, fusion and import were designed and optimised to dissect the mechanism(s) of action of the peptides. Results indicated that the peptides acted upstream of nuclear import of viral ribonucleoprotein complexes but did not reduce overall virus binding to cells. However, the peptides caused aggregation of the virus particles on the surface of the host cells and reduced their internalisation. Further work evaluated how the peptides may be delivered to the site(s) of viral replication in poultry. A screen of the current literature was completed to allow for the design of an expression cassette for poultry-derived Lactobacillus to express FluPep and Entry Blocker. Though the cassette has been reported to be suitable for expression of heterologous proteins in Lactobacilli, rescue of recombinants for expression of anti-viral peptides or a reporter protein proved challenging, possibly owing to toxicity. A stable construct for the expression of FluPep 4 in Lactobacillus was obtained but culture supernatant did not inhibit virus replication.

Subjects/Keywords: 616.9; antiviral peptide; FluPep; influenza

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

APA (6^th Edition):

Jasim, S. N. (2016). The characterisation of a novel family of peptides with potent anti-viral activity against influenza viruses. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/25396

Chicago Manual of Style (16^th Edition):

Jasim, Seema Naseralla. “The characterisation of a novel family of peptides with potent anti-viral activity against influenza viruses.” 2016. Doctoral Dissertation, University of Edinburgh. Accessed April 13, 2021. http://hdl.handle.net/1842/25396.

MLA Handbook (7^th Edition):

Jasim, Seema Naseralla. “The characterisation of a novel family of peptides with potent anti-viral activity against influenza viruses.” 2016. Web. 13 Apr 2021.

Vancouver:

Jasim SN. The characterisation of a novel family of peptides with potent anti-viral activity against influenza viruses. [Internet] [Doctoral dissertation]. University of Edinburgh; 2016. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/1842/25396.

Council of Science Editors:

Jasim SN. The characterisation of a novel family of peptides with potent anti-viral activity against influenza viruses. [Doctoral Dissertation]. University of Edinburgh; 2016. Available from: http://hdl.handle.net/1842/25396

University of Edinburgh

10. Bacon, Matthew Neil. An antiviral peptide targeting influenza and parainfluenza.

Degree: PhD, 2014, University of Edinburgh

URL: http://hdl.handle.net/1842/17861

► Respiratory virus infections, such as those caused by influenza, parainfluenza and respiratory syncytial virus (hRSV), continue to be a major cause of morbidity and mortality… (more)

▼ Respiratory virus infections, such as those caused by influenza, parainfluenza and respiratory syncytial virus (hRSV), continue to be a major cause of morbidity and mortality in both the developed and developing world. Currently, the main means of control of influenza virus infection is vaccination, which requires advanced knowledge of the strain that will be prevalent each year. Alternative strategies involve the use of anti-viral drugs, which function primarily as a prophylactic. Currently, there are five main drugs available against influenza, the adamantanes (amantadine and rimantidine) and the neuraminidase inhibitors (oseltamivir, zanamivir and peramivir). However, major problems exist with antivirals, notably the development of drug resistance. This means that new drugs are urgently required that also satisfy the need to intervene at specific phases of the infection. This thesis describes the development of a peptide with anti-influenza virus activity (Flupep), from which a library of closely related peptides were synthesised, with the aim of optimising antiviral efficacy. Peptides were tested in vitro using a plaque reduction assay on cultured cell lines, Vero and MDCK for parainfluenza and influenza respectively. Two strains of influenza and two of parainfluenza were used, covering the main subtypes that infect humans: Influenza A, Influenza B, PIV2 and PIV3. The plaque assay involved mixing a fixed dose of virus with dilutions of peptide and infecting the cultured cells, followed by incubation for between 3 and 14 days. The cells were then fixed, stained and plaques counted as a measure of viral infectivity. Previous work had shown that Flupep both interacts with haemagglutinin and is an antagonist of inflammatory cytokines. As a possible explanation for antiviral activity, binding affinity of the peptide to haemagglutinin was measured utilising enzyme linked immunosorbent assays. However, significant binding was not detected, suggesting non-specific binding and anti-inflammatory potential are more important routes for antiviral activity. Peptides which demonstrated greater than 90% plaque knockdown in vitro were evaluated in vivo. Anaesthetised mice were infected with influenza A and administered with the peptide concurrently. Following infection, body weights were measured daily and clinical signs, such as shortness of breath, quality of coat and posture, were monitored as indicators of overall health. Most mice were culled on the seventh day post-infection and lung viral titres were determined using a plaque assay. Two peptides were identified with high efficacy against influenza. These peptides, when used in vivo, improved clinical signs of and dramatically reduced levels of infectious virus in the lungs by 7 days post infection. The peptide with highest efficacy was PEGylated and subsequently shown to possess therapeutic potential. Intranasal administration of the PEG-peptide to anaesthetised mice, on the two days subsequent to infection with influenza A, revealed a 17-fold fall in lung viral titres by…

Subjects/Keywords: 616.2; influenza; flu; antiviral; peptides

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

APA (6^th Edition):

Bacon, M. N. (2014). An antiviral peptide targeting influenza and parainfluenza. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/17861

Chicago Manual of Style (16^th Edition):

Bacon, Matthew Neil. “An antiviral peptide targeting influenza and parainfluenza.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed April 13, 2021. http://hdl.handle.net/1842/17861.

MLA Handbook (7^th Edition):

Bacon, Matthew Neil. “An antiviral peptide targeting influenza and parainfluenza.” 2014. Web. 13 Apr 2021.

Vancouver:

Bacon MN. An antiviral peptide targeting influenza and parainfluenza. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/1842/17861.

Council of Science Editors:

Bacon MN. An antiviral peptide targeting influenza and parainfluenza. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/17861

Rutgers University

11. Sawant, Rajlakshmi, 1992-. Synthesis and development of small molecule inhibitors targeting viral PAn endonuclease and bacterial MreB.

Degree: MS, Medicinal Chemistry, 2018, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/57690/

► Imminent threat of pandemics of influenza, along with increasing resistance of the virus to existing anti-viral drugs has posed a need for development of an… (more)

▼ Imminent threat of pandemics of influenza, along with increasing resistance of the virus to existing anti-viral drugs has posed a need for development of an anti-viral that possesses a novel mechanism of action. PAN Endonuclease enzyme protein plays an important role in influenza A viral transcription with the cap-snatching process being highly conserved in the virus. This makes PAN an attractive target for drug development. Our efforts began with fragment screening to identify an effective pharmacophore. 5-chloro-3-hydroxypyridin-2(1H)-one was identified as a highly active chelating ligand at the endonuclease site containing metal ions. After extensive research, 3-hydroxypyridin-2(1H)-ones, 3-hydroxyquinolin-2(1H)-ones and aza analogs of 3-hydroxypyridin-2(1H)-ones were prepared which displayed modest enzymatic inhibitory activity. This activity didn’t translate in the cellular assay. Hence, we synthesized a known endonuclease inhibitor (Shionogi Co.) to check whether the established structure activity relationships were “false-positive” data. We also experimented with the development of isatin derivatives to continue the search for a lead compound. The most promising compound, 6-Bromo-1-hydroxyindoline-2,3-dione showed 45% inhibition at 200 μM concentration. This molecule was optimized to give 6-(4-fluorophenyl)-1,3-dihydroxy-3-methylindolin-2-one which showed no inhibitory activity in the enzyme assay. Despite of unsuccessful attempts, continued efforts are being made to explore PAN as a potential target for antiviral therapy. Our research efforts were then directed towards tackling another emerging global health crisis, the antibiotic resistance crisis. With increasing bacterial strains developing resistance towards currently available antibiotics, there is a need to target a novel mechanism of action in bacteria. MreB, a highly conserved actin homologue in bacteria is important in cell wall synthesis and determining the cell shape in bacteria. The significance of MreB in bacterial cell growth makes it a lucrative target for design of antibiotics. A22 was identified as an MreB inhibitor with modest inhibitory activity. Our efforts were focused on studying the structure activity relationships by modifying the aromatic core of A22. A series of benzothiophene, benzofuran and indole based isothioureas was synthesized. Deductions made from SAR studies are currently being used to develop an optimized lead that can show substantial MreB inhibitory activity and can further be developed into clinic. Advisors/Committee Members: LaVoie, Edmond J (chair), Hu, Longqin (internal member), Rice, Joseph E (internal member), School of Graduate Studies.

Subjects/Keywords: Influenza A virus; Antiviral agents

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

APA (6^th Edition):

Sawant, Rajlakshmi, 1. (2018). Synthesis and development of small molecule inhibitors targeting viral PAn endonuclease and bacterial MreB. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/57690/

Chicago Manual of Style (16^th Edition):

Sawant, Rajlakshmi, 1992-. “Synthesis and development of small molecule inhibitors targeting viral PAn endonuclease and bacterial MreB.” 2018. Masters Thesis, Rutgers University. Accessed April 13, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/57690/.

MLA Handbook (7^th Edition):

Sawant, Rajlakshmi, 1992-. “Synthesis and development of small molecule inhibitors targeting viral PAn endonuclease and bacterial MreB.” 2018. Web. 13 Apr 2021.

Vancouver:

Sawant, Rajlakshmi 1. Synthesis and development of small molecule inhibitors targeting viral PAn endonuclease and bacterial MreB. [Internet] [Masters thesis]. Rutgers University; 2018. [cited 2021 Apr 13]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/57690/.

Council of Science Editors:

Sawant, Rajlakshmi 1. Synthesis and development of small molecule inhibitors targeting viral PAn endonuclease and bacterial MreB. [Masters Thesis]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/57690/

12. Barroso, Lana Karine Vasconcelos. Atividade antiviral in vitro de plantas medicinais da flora cearense contra o vírus da dengue.

Degree: 2015, Universidade de Fortaleza; Mestrado Em Saúde Coletiva; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu

URL: https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=96199 ; http://dspace.unifor.br/handle/tede/96199

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Made available in DSpace on 2021-03-20T00:04:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-10-29

Dengue is an infectious, tropical and endemic disease. Dengue demands… (more)

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Made available in DSpace on 2021-03-20T00:04:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-10-29

Dengue is an infectious, tropical and endemic disease. Dengue demands numerous efforts aimed at its prevention and control. The lack of an effective vaccine as well as specific treatment to combat the virus has encouraged the development of research to verify products with antiviral activity, especially the use of natural products. This study aimed to evaluate the antiviral activity in vitro of medicinal plants of Ceará flora against serotypes 2 and 3 of the dengue virus. In search of ethanol extracts were used Acrocomia aculeata (Jacq.) Lood. ex Mart, Azadirachta indica A. Juss, Cajanus cajan (L.) Millsp., Caryocar coriaceum wittm, Mormodica charantia L., Plectranthus amboinicus (Lour.), Schinus terebinthifolius Raddi, Ximenia americana L. and the essential oil of Eugenia jambolana (Lam.) and Vanillosmopsis arborea Baker (1000; 500; 250; 125; 62,5 e 31,25 ?g/mL). In the early stages of evaluation tests were performed cytotoxicity of samples in Vero cells. Then the screening of antiviral activity was performed with the non-cytotoxic samples and used three methodological strategies (pre-treatment, post-treatment and virucidal) and different time points were tested (1000, 500 and 250 ?g/mL) compared to viral infection. Only the Azadirachta indica (CC50 197.0 ?g/mL), Cajanus cajan (CC50 156.5 ?g/mL) and Caryocar coriaceum (CC50 199.4 ?g/mL) showed cytotoxic potential. The remaining plants even at the highest concentration tested (1000 ?g/mL), did not exert cytotoxicity at least 50% of the monolayer and were used in subsequent stages of the search. The screening of antiviral activity found that the ethanol extracts of Acrocomia aculeata (Jacq.) Lood. ex Mart and Plectranthus amboinicus (Lour.) developed antiviral action against DENV-2 in all valuation techniques performed in this study, a fact that may be related to the presence of tannins and flavonoids. The essential oil Vanillosmopsis arborea Baker, rich in alpha-bisabolol, inhibited the virus through all valuation techniques, except for pre-treatment against DENV-3, suggesting viral inhibition in the early and late stages of the cycle replicative. These plants here identified as potential antiviral against dengue virus have already been studied in other surveys which cited its antimicrobial and antiviral actions. The findings of this screening revealed promising plants in the investigation of an antiviral drug against dengue virus, especially the ethanol extracts of Acrocomia aculeata (Jacq.) Lood.; the Plectranthus amboinicus (Lour.) and the essential oil of Vanillosmopsis arborea Bake. The essential oil of Vanillosmopsis arborea Baker and Plectranthus amboinicus (Lour.) are nontoxic to mammalian last and detaining potential inhibition of DENV cells, suggesting the feasibility of further research as its antiviral activity and more precise elucidation of mechanism of action.

A dengue é uma doença infecciosa, tropical e de caráter endêmico a qual…

Advisors/Committee Members: Barros, Adriana Rolim Campos, Lima, Danielle Malta, Nogueira, Nadia Accioly Pinto, Lima, Danielle Malta, Barros, Adriana Rolim Campos.

Subjects/Keywords: Antiviral; Plantas medicinais; Dengue

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

APA (6^th Edition):

Barroso, L. K. V. (2015). Atividade antiviral in vitro de plantas medicinais da flora cearense contra o vírus da dengue. (Masters Thesis). Universidade de Fortaleza; Mestrado Em Saúde Coletiva; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu. Retrieved from https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=96199 ; http://dspace.unifor.br/handle/tede/96199

Chicago Manual of Style (16^th Edition):

Barroso, Lana Karine Vasconcelos. “Atividade antiviral in vitro de plantas medicinais da flora cearense contra o vírus da dengue.” 2015. Masters Thesis, Universidade de Fortaleza; Mestrado Em Saúde Coletiva; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu. Accessed April 13, 2021. https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=96199 ; http://dspace.unifor.br/handle/tede/96199.

MLA Handbook (7^th Edition):

Barroso, Lana Karine Vasconcelos. “Atividade antiviral in vitro de plantas medicinais da flora cearense contra o vírus da dengue.” 2015. Web. 13 Apr 2021.

Vancouver:

Barroso LKV. Atividade antiviral in vitro de plantas medicinais da flora cearense contra o vírus da dengue. [Internet] [Masters thesis]. Universidade de Fortaleza; Mestrado Em Saúde Coletiva; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu; 2015. [cited 2021 Apr 13]. Available from: https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=96199 ; http://dspace.unifor.br/handle/tede/96199.

Council of Science Editors:

Barroso LKV. Atividade antiviral in vitro de plantas medicinais da flora cearense contra o vírus da dengue. [Masters Thesis]. Universidade de Fortaleza; Mestrado Em Saúde Coletiva; UNIFOR; Brasil; Divisão de Pós Graduação Stricto Sensu; 2015. Available from: https://uol.unifor.br/oul/ObraBdtdSiteTrazer.do?method=trazer&ns=true&obraCodigo=96199 ; http://dspace.unifor.br/handle/tede/96199

Universidade Federal de Viçosa

13. Fernanda Souza de Oliveira. Atividade antiviral da quercetina sobre alguns vírus de importância veterinária.

Degree: 2007, Universidade Federal de Viçosa

URL: http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=987

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A busca por novas substâncias com potencial antimicrobiano se torna crescente e se faz necessário devido, principalmente, ao desenvolvimento de resistência de agentes infecciosos às… (more)

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A busca por novas substâncias com potencial antimicrobiano se torna crescente e se faz necessário devido, principalmente, ao desenvolvimento de resistência de agentes infecciosos às drogas atuais. Compostos naturais, dentre eles os flavonóides, tem sido uma fonte particularmente rica desses agentes anti-infectivos. O objetivo deste trabalho foi o de avaliar o potencial antiviral do flavonóide quercetina contra o Parvovírus Canino (CPV), Herpesvírus Bovino 5 (BoHV-) e Herpesvírus Eqüino 1 (EHV-1). Ensaios in vitro foram realizados, como o ensaio de Inativação Direta (AID), no qual se incubou a quercetina com o vírus antes da inoculação, ensaio End Point onde foi feito um prétratamento das células com a quercetina e o ensaio denominado de Timing of Addition, onde foi feito o tratamento das células em cada passo da infecção viral. Foi observado que a atividade antiviral da quercetina parece ser nos passos iniciais da infecção, principalmente no momento da adsorção viral. Nos ensaios com o Parvovírus Canino e o Herpesvírus Eqüino 1, a quercetina demonstrou se ligar a receptores celulares, enquanto que nos ensaios com o Herpesvírus Bovino 5, a ação da quercetina demonstrou ser na ligação a estruturas presentes no envelope viral. Nos ensaios in vivo realizados com os BoHV-5 e EHV-1, foi possível avaliar a ação direta da quercetina sobre a infectividade viral e a sua atuação em outros mecanismos de defesa do animal. A partir dos resultados encontrados neste trabalho, sugerimos que a quercetina possa atuar como um possível agente antiviral, não somente por atuar de forma direta no controle da infecção viral, mas também por meio da ativação de múltiplos processos que indiretamente promovem o controle da infecção viral pelo organismo.

The search for new substances with potential antimicrobials is growing and is necessary due, mainly, to the development of resistance of infectious agents to the current drugs. Natural compounds, among them flavonoids, have been a particularly rich source of these antimicrobial agents. The objective of this work was to evaluate the antiviral potential of flavonoid quercetin against Canine Parvovirus (CPV), Bovine Herpesvirus 5 (BoHV-5) and Equid Herpesvirus 1 (EHV-1). Assays in vitro were accomplished, as the assay inativating direct (AID), in which the quercetin was incubated with the virus before the inoculation, assay End Point in which quercetin was incubated with the cells before viral inoculation and the assay Timing of addtion, in which treatment of the cells was made in each step of infection. It was observed that the antiviral activity of quercetin seems to be in the initial steps of the viral infection, mainly at the moment of viral attachment. In the assays with Canine Parvovírus, quercetin demonstrated to bind the cellular receptors, whereas in the assays with the Herpesvirus used in this study, the performance of the quercetin demonstrated to be in the linking the structures of the viral envelope. In the assays in vivo with BoHV-5 and EHV-1, was possible to evaluate the direct…

Advisors/Committee Members: Maria Cristina Baracat Pereira, Márcia Rogéria de Almeida Lamêgo, Joaquín Hernán Patarroyo Salcedo, Marlene Isabel Vargas Viloria, Tânia Toledo de Oliveira, João Paulo Viana Leite.

Subjects/Keywords: BIOQUIMICA; Atividade antiviral; Quercetina; Vírus; Antiviral activity; Quercetin; Virus

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APA (6^th Edition):

Oliveira, F. S. d. (2007). Atividade antiviral da quercetina sobre alguns vírus de importância veterinária. (Thesis). Universidade Federal de Viçosa. Retrieved from http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=987

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):

Oliveira, Fernanda Souza de. “Atividade antiviral da quercetina sobre alguns vírus de importância veterinária.” 2007. Thesis, Universidade Federal de Viçosa. Accessed April 13, 2021. http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=987.

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

MLA Handbook (7^th Edition):

Oliveira, Fernanda Souza de. “Atividade antiviral da quercetina sobre alguns vírus de importância veterinária.” 2007. Web. 13 Apr 2021.

Vancouver:

Oliveira FSd. Atividade antiviral da quercetina sobre alguns vírus de importância veterinária. [Internet] [Thesis]. Universidade Federal de Viçosa; 2007. [cited 2021 Apr 13]. Available from: http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=987.

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

Council of Science Editors:

Oliveira FSd. Atividade antiviral da quercetina sobre alguns vírus de importância veterinária. [Thesis]. Universidade Federal de Viçosa; 2007. Available from: http://www.tede.ufv.br/tedesimplificado/tde_busca/arquivo.php?codArquivo=987

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

14. Ould Sidi Mohamed, Bemba. Synthèse de carbonucléosides phosphonates à visée antivirale : Synthesis of carbonucleotides phosphonates as potential antiviral agents.

Degree: Docteur es, Ingénierie biomoléculaire, 2016, Montpellier

URL: http://www.theses.fr/2016MONTT234

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Les analogues de nucléosides ont été largement utilisés dans le traitement d’affections d’origine virale grâce à l’activité biologique de ces dérivés. Nous nous sommes particulièrement… (more)

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Les analogues de nucléosides ont été largement utilisés dans le traitement d’affections d’origine virale grâce à l’activité biologique de ces dérivés. Nous nous sommes particulièrement intéressés dans ce travail à l’étude de carbonucléosides phosphonates. Le premier chapitre de cette thèse rapporte une étude bibliographique sur les virus et les analogues nucléosidiques approuvés par la FDA. Les mécanismes d’action de ces analogues ont été également abordés dans ce chapitre. Dans le deuxième chapitre, nous avons décrit la synthèse des dérivés 2’- ou 4’-hydroxy-4’-carbonucléoside méthyle phosphonates en série d’adénine et guanine. Le troisième chapitre est consacré à la mise au point d’une réaction d’hydrophosphonylation sous irradiation UV d’alcènes/alcynes conduisant aux alkyle/vinyle phosphonates correspondants. Enfin, le dernier chapitre présente la synthèse des dérivés 4’-hydroxy-4’-carbonucléosides éthyle phosphonates utilisant la méthodologie développée dans le troisième chapitre. Tous les carbonucléosides phosphonates synthétisés sont en cours d’évaluation biologique.

Nucleoside analogues have been widely used in the treatment of viral diseases owing to biological activity of these derivatives. We are particularly interested in carbonucleosides phosphonates. The first chapter of this thesis reports on a bibliographic study on viruses and on nucleosidic analogues approved by FDA for medical use. Antiviral mechanisms of action were also discussed in this chapter. In the second chapter, we described the synthesis of derivatives 2’- or 4’-hydroxy-4’-methyl carbonucleoside phosphonate in adenine and guanine series. The third chapter is devoted to the development of a hydrophosphonylation reaction under UV irradiation of alkenes/alkyne leading to the alkyl/vinyl corresponding phosphonates. Finally, the last chapter presents the synthesis of derivatives 4’-hydroxy-4’-ethyl carbonucleosides phosphonates using the methodology developed in the third chapter. All carbonucleoside phosphonates synthesized are ongoing biological evaluation.

Advisors/Committee Members: Mathé, Christophe (thesis director).

Subjects/Keywords: Carbonucléosides; Phosphonates; Antiviral; Hydrophosphonylation; Carbonucleosides; Phosphonates; Antiviral; Hydrophosphonylation

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APA (6^th Edition):

Ould Sidi Mohamed, B. (2016). Synthèse de carbonucléosides phosphonates à visée antivirale : Synthesis of carbonucleotides phosphonates as potential antiviral agents. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2016MONTT234

Chicago Manual of Style (16^th Edition):

Ould Sidi Mohamed, Bemba. “Synthèse de carbonucléosides phosphonates à visée antivirale : Synthesis of carbonucleotides phosphonates as potential antiviral agents.” 2016. Doctoral Dissertation, Montpellier. Accessed April 13, 2021. http://www.theses.fr/2016MONTT234.

MLA Handbook (7^th Edition):

Ould Sidi Mohamed, Bemba. “Synthèse de carbonucléosides phosphonates à visée antivirale : Synthesis of carbonucleotides phosphonates as potential antiviral agents.” 2016. Web. 13 Apr 2021.

Vancouver:

Ould Sidi Mohamed B. Synthèse de carbonucléosides phosphonates à visée antivirale : Synthesis of carbonucleotides phosphonates as potential antiviral agents. [Internet] [Doctoral dissertation]. Montpellier; 2016. [cited 2021 Apr 13]. Available from: http://www.theses.fr/2016MONTT234.

Council of Science Editors:

Ould Sidi Mohamed B. Synthèse de carbonucléosides phosphonates à visée antivirale : Synthesis of carbonucleotides phosphonates as potential antiviral agents. [Doctoral Dissertation]. Montpellier; 2016. Available from: http://www.theses.fr/2016MONTT234

15. Paganini, Éder Ramos [UNESP]. Síntese e atividade anti-HCV, anti-candida e antibacteriana de nitrochalconas.

Degree: 2016, Universidade Estadual Paulista (UNESP)

URL: http://hdl.handle.net/11449/137815

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Não recebi financiamento

Chalconas são flavonoides de cadeia aberta com uma cetona α,β-insaturada, a qual separa duas subunidades fenílicas (anéis A e B). Estas substâncias podem ser sintetizadas pela condensação de Claisen-Schmidt e apresentam inúmeras atividades biológicas, tais como; antioxidante, anti-inflamatória, antimicrobiana e antitumoral. O presente trabalho objetivou a síntese de uma série de 21 chalconas contendo o grupo nitro em diferentes posições nos anéis A e B. A síntese das substâncias foi realizada pela condensação aldólica sob catálise com ácido sulfúrico e ácido acético como solvente, demonstrando rendimentos que variaram de 63 a 97%. As purificações das nitrochalconas foram realizadas por técnicas cromatográficas, tais como; Cromatografia em Coluna de Fase Normal (gel de sílica) e Cromatografia de Permeação em Gel (Sephadex, LH-20). A confirmação estrutural das substâncias foi realizada por meio da análise dos espectros de RMN de 1H e de 13C. A Hepatite C se apresenta como uma doença de grande incidência na população mundial e pode levar a carcinoma hepatocelular. Essa doença é causada pelo vírus da Hepatite C (HCV). A substância E.08 (2-hidroxi-5-flúor-4’-nitrochalcona) inédita na literatura,foi capaz de inibir a replicação do HCV em 30% a 2 µmol L 1, segundo ensaio de luciferase. A candidíase é uma infecção fúngica causada por leveduras do gênero Candida. A substância E.23 (3’-nitrochalcona) demonstrou atividade anti-Candida, exibindo valores de CIM de 0,97 µg mL-1 contra C. albicans. As bactérias são responsáveis por inúmeras doenças ao homem. A substância E.47 (2-hidroxi-5-nitrochalcona) demonstra atividade anti-Staphylococcus aureus e anti-Staphylococcus aureus resistente à meticilina (MRSA), exibindo valores de CIM de 0,97 e 1,95 µg mL-1 respectivamente.

Chalcones are opened-chain flavonoids, bearing an α,β-unsaturated ketone, which separates two phenyl subunits (rings A and B). These 21 compounds have been synthesized by Claisen-Schmidt condensation reactions. They exhibit several biological activities, such as antioxidant, anti-inflammatory, antimicrobial and antitumoral. The current work aimed the synthesis of two series of 21 chalcones containing nitro group at A and B rings. Synthetic procedures used aldol condensation under sulfuric acid catalysis and acetic acid as solvent, with yield ranging from 63 to 97%. Purification of crude products was…

Advisors/Committee Members: Universidade Estadual Paulista (UNESP), Regasini, Luis Octavio [UNESP].

Subjects/Keywords: Chalcona; Antiviral; Antifúngico; Antibacteriano; Flavonoide; Chalcone; Flavonoid; Antiviral; Antifungal; Antibacterial

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

APA (6^th Edition):

Paganini, �. R. [. (2016). Síntese e atividade anti-HCV, anti-candida e antibacteriana de nitrochalconas. (Masters Thesis). Universidade Estadual Paulista (UNESP). Retrieved from http://hdl.handle.net/11449/137815

Chicago Manual of Style (16^th Edition):

Paganini, Éder Ramos [UNESP]. “Síntese e atividade anti-HCV, anti-candida e antibacteriana de nitrochalconas.” 2016. Masters Thesis, Universidade Estadual Paulista (UNESP). Accessed April 13, 2021. http://hdl.handle.net/11449/137815.

MLA Handbook (7^th Edition):

Paganini, Éder Ramos [UNESP]. “Síntese e atividade anti-HCV, anti-candida e antibacteriana de nitrochalconas.” 2016. Web. 13 Apr 2021.

Vancouver:

Paganini �R[. Síntese e atividade anti-HCV, anti-candida e antibacteriana de nitrochalconas. [Internet] [Masters thesis]. Universidade Estadual Paulista (UNESP); 2016. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/11449/137815.

Council of Science Editors:

Paganini �R[. Síntese e atividade anti-HCV, anti-candida e antibacteriana de nitrochalconas. [Masters Thesis]. Universidade Estadual Paulista (UNESP); 2016. Available from: http://hdl.handle.net/11449/137815

Universiteit Utrecht

16. Stapels, D.A.C. Exploring the mechanism behind Wolbachia-mediated antiviral immunity in Drosophila melanogaster.

Degree: 2010, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/179395

► The intracellular bacterium Wolbachia pipientis is widely spread amongst insect populations, like Drosophila. Recently, Wolbachia infection was found to reduce virus-induced mortality and lower the… (more)

▼ The intracellular bacterium Wolbachia pipientis is widely spread amongst insect populations, like Drosophila. Recently, Wolbachia infection was found to reduce virus-induced mortality and lower the viral load in dually infected Drosophila melanogaster. Unravelling the mechanism behind this Wolbachia-induced survival might further elucidate the high prevalence of Wolbachia amongst insect species; but above all it might give new insights in antiviral immunity of insects that spread vector-borne diseases and it might help to better understand antiviral immunity in general. Even thought Wolbachia infection does not induce a clear phenotype in D. melanogaster, it does result in profound changes in transcription, for example of signaling molecules in the Toll, Imd, and JNK pathways. In addition, heat shock proteins, autophagy, and other processes – possibly induced by secreted Ankyrin-repeat-containing proteins of Wolbachia – might be active during Wolbachia infection. Wolbachia was shown to protect against positive sense (+) single-stranded RNA viruses from different families that replicate in association with cellular membranes. These viruses normally promote antiviral RNA interference, Imd and Jak/STAT signaling, autophagy, phagocytosis, and/or apoptosis in Drosophila. Remarkably, Wolbachia does not protect against infection with a double-stranded DNA virus. Unfortunately, little is known about the reactions induced upon double-stranded DNA-virus infection. All together, Wolbachia might protect Drosophila by priming the antiviral immune response, for example by activating Imd and Toll signaling. Importantly, all examined RNA viruses show overlapping cell tropism with Wolbachia, thus Wolbachia might also directly affect viral replication. For example, Wolbachia could slow down viral replication by competing for cellular nutrients, affect vesicle transport, or secrete proteins detrimental to the viruses. Additional research will unravel the mechanism behind the Wolbachia-induced antiviral immunity in Drosophila and the occurrence of this phenomenon amongst other species. Advisors/Committee Members: van Rij, R..

Subjects/Keywords: Geneeskunde; Wolbachia; Drosophila; ssRNA virus; antiviral immunity

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APA (6^th Edition):

Stapels, D. A. C. (2010). Exploring the mechanism behind Wolbachia-mediated antiviral immunity in Drosophila melanogaster. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/179395

Chicago Manual of Style (16^th Edition):

Stapels, D A C. “Exploring the mechanism behind Wolbachia-mediated antiviral immunity in Drosophila melanogaster.” 2010. Masters Thesis, Universiteit Utrecht. Accessed April 13, 2021. http://dspace.library.uu.nl:8080/handle/1874/179395.

MLA Handbook (7^th Edition):

Stapels, D A C. “Exploring the mechanism behind Wolbachia-mediated antiviral immunity in Drosophila melanogaster.” 2010. Web. 13 Apr 2021.

Vancouver:

Stapels DAC. Exploring the mechanism behind Wolbachia-mediated antiviral immunity in Drosophila melanogaster. [Internet] [Masters thesis]. Universiteit Utrecht; 2010. [cited 2021 Apr 13]. Available from: http://dspace.library.uu.nl:8080/handle/1874/179395.

Council of Science Editors:

Stapels DAC. Exploring the mechanism behind Wolbachia-mediated antiviral immunity in Drosophila melanogaster. [Masters Thesis]. Universiteit Utrecht; 2010. Available from: http://dspace.library.uu.nl:8080/handle/1874/179395

University of Hong Kong

17. Mak, Ka-ki, Peter. The potential trade-offs between treatment and prophylaxis with antivirals in households during a pandemic.

Degree: 2007, University of Hong Kong

URL: http://hdl.handle.net/10722/50780

Subjects/Keywords: Epidemics.; Antiviral agents.

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

APA (6^th Edition):

Mak, Ka-ki, P. (2007). The potential trade-offs between treatment and prophylaxis with antivirals in households during a pandemic. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/50780

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):

Mak, Ka-ki, Peter. “The potential trade-offs between treatment and prophylaxis with antivirals in households during a pandemic.” 2007. Thesis, University of Hong Kong. Accessed April 13, 2021. http://hdl.handle.net/10722/50780.

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

MLA Handbook (7^th Edition):

Mak, Ka-ki, Peter. “The potential trade-offs between treatment and prophylaxis with antivirals in households during a pandemic.” 2007. Web. 13 Apr 2021.

Vancouver:

Mak, Ka-ki P. The potential trade-offs between treatment and prophylaxis with antivirals in households during a pandemic. [Internet] [Thesis]. University of Hong Kong; 2007. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10722/50780.

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

Council of Science Editors:

Mak, Ka-ki P. The potential trade-offs between treatment and prophylaxis with antivirals in households during a pandemic. [Thesis]. University of Hong Kong; 2007. Available from: http://hdl.handle.net/10722/50780

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

McMaster University

18. Chiang, Christopher. NOVEL THERAPEUTIC FOR RESPIRATORY SYNCYTIAL VIRUS.

Degree: MSc, 2017, McMaster University

URL: http://hdl.handle.net/11375/23882

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Background: Respiratory syncytial virus (RSV) is one of the leading causes of acute lower respiratory tract infection and childhood hospitalization worldwide. However, there are currently… (more)

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Background: Respiratory syncytial virus (RSV) is one of the leading causes of acute lower respiratory tract infection and childhood hospitalization worldwide. However, there are currently no vaccines or antivirals available to prevent or treat RSV infections. Of the 11 proteins encoded by RSV’s negative-sense single-stranded RNA genome, the nucleoprotein, phosphoprotein, and large polymerase interact through well characterized domains to form the RNA-dependent RNA polymerase complex. This polymerase complex is essential for viral replication and virulence, which makes it an excellent antiviral target. Previous studies have shown that the nucleoprotein-phosphoprotein interaction of the polymerase complex can be disrupted by synthetic peptides of the last 21 C-terminal (P220-241) or the first 29 N-terminal (P1-29) amino acids of the phosphoprotein. Objective: The Mahony lab has also previously demonstrated that P220-241 conjugated to a maltose binding protein (MBP) and HIV-1 Tat cell penetrating peptide (CPP) could inhibit up to 90% of RSV A replication in vitro. However, the bacterial derived MBP is immunogenic. This study builds on these findings by developing and evaluating the efficacy of a P220-241 peptide mimetic conjugated to human thioredoxin (hTrx) carrier protein and a P1-29 peptide mimetic conjugated to MBP. Methods and Results: Inverse PCR and In-Fusion® cloning was used to clone a hTrx-P220-241 plasmid, which was then expressed as a recombinant protein and purified by affinity chromatography for functional analysis. HTrx-P220-241 was shown to specifically interact with RSV nucleoprotein in a glutathione S-transferase (GST) pull down assays and it could successfully enter into LLC-MK2 cells. However, upon challenge with RSV A, LLC-MK2 cells that were incubated with increasing concentrations of hTrx-P220-241 did not inhibit RSV A replication when assessed by indirect immunofluorescence microscopy. The MBP-P1-29 construct did not exhibit any significant cytotoxicity in LLC-MK2 cells nor BEAS-2B cells. Upon challenge with RSV A, LLC-MK2 cells and BEAS-2B cells pre-treated with MBP-P1-29 demonstrated a dose-dependent inhibition of RSV replication in vitro, with a percent inhibition of infection of 80% and 60% respectively. Furthermore, MBP-P1-29 also reduced the release of infectious progeny virion by up to 74% in LLC-MK2 cells and 34% in BEAS-2B cells. Conclusion: Phosphoprotein peptide mimetics targeting essential nucleoprotein-phosphoprotein interaction are a promising approach in the development of therapeutic treatments for RSV. In this study, a P220-241 peptide mimetic conjugated to a human thioredoxin scaffold protein was not able to inhibit RSV A replication while a P1-29 peptide attached to a maltose binding protein was effective in reducing RSV replication in vitro. Thus, further studies are required to evaluate a P1-29 peptide mimetic against different RSV A and B strains and to find an appropriate human carrier protein to attach it to.

Thesis

Master of Science (MSc)

Respiratory syncytial…

Advisors/Committee Members: Mahony, James, Medical Sciences (Molecular Virology and Immunology Program).

Subjects/Keywords: Virology; RSV; peptide mimetic; P1-29; antiviral

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

APA (6^th Edition):

Chiang, C. (2017). NOVEL THERAPEUTIC FOR RESPIRATORY SYNCYTIAL VIRUS. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/23882

Chicago Manual of Style (16^th Edition):

Chiang, Christopher. “NOVEL THERAPEUTIC FOR RESPIRATORY SYNCYTIAL VIRUS.” 2017. Masters Thesis, McMaster University. Accessed April 13, 2021. http://hdl.handle.net/11375/23882.

MLA Handbook (7^th Edition):

Chiang, Christopher. “NOVEL THERAPEUTIC FOR RESPIRATORY SYNCYTIAL VIRUS.” 2017. Web. 13 Apr 2021.

Vancouver:

Chiang C. NOVEL THERAPEUTIC FOR RESPIRATORY SYNCYTIAL VIRUS. [Internet] [Masters thesis]. McMaster University; 2017. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/11375/23882.

Council of Science Editors:

Chiang C. NOVEL THERAPEUTIC FOR RESPIRATORY SYNCYTIAL VIRUS. [Masters Thesis]. McMaster University; 2017. Available from: http://hdl.handle.net/11375/23882

University of Texas Southwestern Medical Center

19. Mata, Miguel Angel. Chemical Inhibition of RNA Viruses Reveals REDD1 as a Host Defense Factor.

Degree: 2013, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/2723

► Influenza (flu) is a contagious infectious respiratory illness. The flu can cause from mild to life-threatening illness. The current therapeutic intervention strategies to prevent or… (more)

▼ Influenza (flu) is a contagious infectious respiratory illness. The flu can cause from mild to life-threatening illness. The current therapeutic intervention strategies to prevent or treat influenza infection are not sufficient in the event that a pathogenic virus strains reaches pandemic proportions. Therefore, the development of anti-influenza therapeutic modalities is critical to respond to a future influenza pandemic. In this study, a chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus (VSV). The mechanism of action occurs through activation of REDD1 expression and concomitant inhibition of mammalian target of rapamycin complex 1 (mTORC1) via TSC1–TSC2 complex. The antiviral activity of naphthalimides was abolished in REDD1−/− cells. Inhibition of REDD1 expression by viruses resulted in activation of the mTORC1 pathway. REDD1-/- cells prematurely upregulated viral proteins via mTORC1 activation and were permissive to virus replication. In contrast, cells conditionally expressing high concentrations of REDD1 downregulated the amount of viral protein. Whole animal studies revealed REDD1-/- mice are highly susceptible to virus infection. Influenza infection of REDD1-/- mice results in decreased TLR7 and MHC class II expression by dendritic cells and macrophages. In addition, excessive inflammatory cell infiltration in the lungs of REDD1-/- infected mice was observed. Preliminary evidence suggests a potential defect in NF-κB signaling upon influenza virus infection in REDD1 deficient mice. Thus, REDD1 is a new host defense factor, and chemical activation of REDD1 expression represents a potent antiviral intervention strategy. Our studies also reveal passage immortalization of REDD1-/- MEFs require loss of the type I IFN response pathway as these cells are unable to induce the expression of interferon genes and interferon inducible genes when challenged with synthetic dsRNA. In contrast, primary or SV40 large T antigen transformed REDD1-/- MEFs activate a type I IFN response when exposed to synthetic dsRNA. Advisors/Committee Members: Roth, Michael G., White, Michael A., Lum, Lawrence, Fontoura, Beatriz.

Subjects/Keywords: Antiviral Agents; Naphthalimides; Orthomyxoviridae; Transcription Factors; Vesiculovirus

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APA (6^th Edition):

Mata, M. A. (2013). Chemical Inhibition of RNA Viruses Reveals REDD1 as a Host Defense Factor. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/2723

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):

Mata, Miguel Angel. “Chemical Inhibition of RNA Viruses Reveals REDD1 as a Host Defense Factor.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed April 13, 2021. http://hdl.handle.net/2152.5/2723.

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

MLA Handbook (7^th Edition):

Mata, Miguel Angel. “Chemical Inhibition of RNA Viruses Reveals REDD1 as a Host Defense Factor.” 2013. Web. 13 Apr 2021.

Vancouver:

Mata MA. Chemical Inhibition of RNA Viruses Reveals REDD1 as a Host Defense Factor. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/2152.5/2723.

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

Council of Science Editors:

Mata MA. Chemical Inhibition of RNA Viruses Reveals REDD1 as a Host Defense Factor. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/2723

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

University of Waikato

20. Zareie, Parvaneh Palma. Honey as an antiviral agent against respiratory syncytial virus .

Degree: 2011, University of Waikato

URL: http://hdl.handle.net/10289/5291

► Respiratory syncytial virus is the most frequent cause of hospitalization for viral respiratory infections in infants and young children worldwide. It also severely affects immunocompromised… (more)

▼ Respiratory syncytial virus is the most frequent cause of hospitalization for viral respiratory infections in infants and young children worldwide. It also severely affects immunocompromised adults and the elderly, however, despite decades of efforts, there is no proven effective treatment for RSV infection and attempts at vaccine development have been hampered by several major obstacles. A large amount of research has established the potent antibacterial activity of honey, but its activity against viral species has been the subject of only a small number of studies. These were with viruses which cause localised infections in which honey could be used topically. Recent studies demonstrating the safety of intrapulmonary administration of honey in sheep and humans raised the possibility of using honey to treat respiratory infections. The aim of this study, therefore, was to extend the knowledge obtained from previous studies of honey’s antiviral activity to its action against RSV. A variety of tests using cell culture were developed to evaluate the susceptibility of RSV to honey. Each test monitored and scored the development of morphological changes to the cells caused by RSV infection to determine whether the honey had any inhibitory effect on these changes. These included tests for: inhibition, where honey was used to treat infected cells; protection, in which the cells were treated with honey prior to infection; neutralisation, in which the virus was directly exposed to the honey for a defined period before being used to inoculate the cells. Pre-treatment of the cells had no effect on the consequent development of cytopathic effect, while the inhibition and neutralisation experiments showed a significant inhibitory effect on the progression of infection, suggesting a direct effect on the virus rather than on the cells, however, further studies are required to confirm this. A wide range of honey types were tested for their inhibitory and neutralising capabilities against RSV and the results suggested that the antiviral activity may be characteristic of more than one type of honey. The activity observed did vary, however, with some types of honey causing greater inhibition of RSV than others. Enzyme-linked immunosorbent assays were also used to quantitatively measure the number of viral antigens in honey-treated and untreated cells. The results confirmed that treatment with honey had caused inhibition of viral replication, there being very little virus detected in honey-treated cells compared with untreated cells infected with RSV. Experiments using quantitative PCR also demonstrated the inhibitory effect of honey on RSV at the transcription level, with significant differences in the mRNA copy numbers of two out of the three viral genes examined. Attempts at isolating the antiviral component in honey demonstrated that the sugar was not responsible for the inhibition of RSV, but that methylglyoxal may play a part in the greater potency of Manuka honeys against RSV. It is concluded from the findings in this study that… Advisors/Committee Members: Molan, Peter C (advisor), Cursons, Raymond T (advisor).

Subjects/Keywords: respiratory syncytial virus; RSV; honey; antiviral

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

APA (6^th Edition):

Zareie, P. P. (2011). Honey as an antiviral agent against respiratory syncytial virus . (Masters Thesis). University of Waikato. Retrieved from http://hdl.handle.net/10289/5291

Chicago Manual of Style (16^th Edition):

Zareie, Parvaneh Palma. “Honey as an antiviral agent against respiratory syncytial virus .” 2011. Masters Thesis, University of Waikato. Accessed April 13, 2021. http://hdl.handle.net/10289/5291.

MLA Handbook (7^th Edition):

Zareie, Parvaneh Palma. “Honey as an antiviral agent against respiratory syncytial virus .” 2011. Web. 13 Apr 2021.

Vancouver:

Zareie PP. Honey as an antiviral agent against respiratory syncytial virus . [Internet] [Masters thesis]. University of Waikato; 2011. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10289/5291.

Council of Science Editors:

Zareie PP. Honey as an antiviral agent against respiratory syncytial virus . [Masters Thesis]. University of Waikato; 2011. Available from: http://hdl.handle.net/10289/5291

University of Texas Southwestern Medical Center

21. Ibarra, Kristie Dawn. Host-Based Mechanisms of Ribavirin Resistance: Implications In Treatment Response of Hepatatis C Virus Infection.

Degree: 2011, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/853

► Many individuals infected with hepatitis C virus (HCV) fail to respond to therapy, resulting in the development of chronic infection and increased risk for fibrosis,… (more)

Subjects/Keywords: Antiviral Agents; Drug Resistance, Viral; Ribavirin; Hepacivirus

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

APA (6^th Edition):

Ibarra, K. D. (2011). Host-Based Mechanisms of Ribavirin Resistance: Implications In Treatment Response of Hepatatis C Virus Infection. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/853

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):

Ibarra, Kristie Dawn. “Host-Based Mechanisms of Ribavirin Resistance: Implications In Treatment Response of Hepatatis C Virus Infection.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed April 13, 2021. http://hdl.handle.net/2152.5/853.

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

MLA Handbook (7^th Edition):

Ibarra, Kristie Dawn. “Host-Based Mechanisms of Ribavirin Resistance: Implications In Treatment Response of Hepatatis C Virus Infection.” 2011. Web. 13 Apr 2021.

Vancouver:

Ibarra KD. Host-Based Mechanisms of Ribavirin Resistance: Implications In Treatment Response of Hepatatis C Virus Infection. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/2152.5/853.

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

Council of Science Editors:

Ibarra KD. Host-Based Mechanisms of Ribavirin Resistance: Implications In Treatment Response of Hepatatis C Virus Infection. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/853

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

University of Arizona

22. Musharrafieh, Rami. New Insights into the Mechanisms of Antiviral Resistance and Action .

Degree: 2020, University of Arizona

URL: http://hdl.handle.net/10150/642021

► Due to the error-prone nature of viral replication, antiviral drugs can select for drug-resistant strains. Understanding the determinants for drug resistance is useful for the… (more)

▼ Due to the error-prone nature of viral replication, antiviral drugs can select for drug-resistant strains. Understanding the determinants for drug resistance is useful for the preclinical evaluation of antivirals, and provides important insight into the biochemical nature of the target. The first part of this dissertation describes studies designed to investigate properties of antiviral drug resistance using a well-established drug target from the influenza A virus as a model protein. The second part of the dissertation mainly focuses on the validation of a novel drug target for a re-emerging virus using biochemical and viral replication assays. Influenza A viruses are pernicious human pathogens that lead to seasonal and pandemic outbreaks. Amantadine and rimantadine are two FDA-approved drugs that target a viral proton channel called M2. These two therapeutics are no longer used due to the emergence of drug resistance. The two principal mutations that give rise to resistance in circulating strains are the S31N and V27A found within the pore of M2. Structural characterization of M2 has guided efforts to target these individual drug resistant channels through the conjugation of the adamantane group, and it was shown that the best V27A inhibitor has in vivo activity, and that the best S31N inhibitor displayed favorable pharmacokinetic properties. Although the determinants of drug resistance for amantadine and rimantadine have been thoroughly investigated, similar studies have not been performed for inhibitors of the V27A and S31N variants. Due to the fine-tuned function and structure of M2, I have hypothesized that V27A and S31N inhibitors would have a high genetic barrier to drug resistance. Using representative V27A and S31N inhibitors, I performed serial passage experiments in cell culture to select for drug-resistant influenza A viruses. Sequencing of the M2 gene segment identified mutations in the channel that gave rise to resistance, which were confirmed using recombinant viruses. In collaboration, functional assays and molecular dynamics simulations were performed to characterize the biophysical and biochemical properties of each mutation. Overall, I discovered that there are at least three mutational strategies for resistance that are selected: 1) mutations in pore-lining residues, 2) mutations in residues lining the interhelical region, and 3) mutations in the C-end of the channel below the tryptophan gate. Analysis of each mutation reveals unique effects on viral fitness, channel function, structural flexibility, pore hydration, and pore size. These studies reveal the utility of cell culture passage experiments in evaluating drug resistance, and provide insights into the mutational landscape of M2 in actively replicating influenza A viruses. The second part of this dissertation mainly focuses on the validation of a drug target from enterovirus D68, a re-emerging virus linked with neurological disease in children. No antivirals are currently available for EV-D68 infections, and few viral proteins have been… Advisors/Committee Members: Brown, Michael F (advisor), Wang, Jun (advisor), Montfort, William R. (committeemember), Cordes, Matthew (committeemember), Horton, Nancy C. (committeemember).

Subjects/Keywords: Antiviral; Drug Resistance; Influenza; M2 Channel

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APA (6^th Edition):

Musharrafieh, R. (2020). New Insights into the Mechanisms of Antiviral Resistance and Action . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/642021

Chicago Manual of Style (16^th Edition):

Musharrafieh, Rami. “New Insights into the Mechanisms of Antiviral Resistance and Action .” 2020. Doctoral Dissertation, University of Arizona. Accessed April 13, 2021. http://hdl.handle.net/10150/642021.

MLA Handbook (7^th Edition):

Musharrafieh, Rami. “New Insights into the Mechanisms of Antiviral Resistance and Action .” 2020. Web. 13 Apr 2021.

Vancouver:

Musharrafieh R. New Insights into the Mechanisms of Antiviral Resistance and Action . [Internet] [Doctoral dissertation]. University of Arizona; 2020. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10150/642021.

Council of Science Editors:

Musharrafieh R. New Insights into the Mechanisms of Antiviral Resistance and Action . [Doctoral Dissertation]. University of Arizona; 2020. Available from: http://hdl.handle.net/10150/642021

University of Debrecen

23. Trinh, GiaKhanh. Direct-acting antiviral in the treatment of hepatitis c virus: a review of pharmacology and clinical application .

Degree: DE – Általános Orvostudományi Kar, University of Debrecen

URL: http://hdl.handle.net/2437/242816

► HCV is a global public health issue with millions people affected around the world. Chronic HCV infection can lead to severe long-term consequences like cirrhosis,… (more)

Subjects/Keywords: Direct-acting antiviral

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APA (6^th Edition):

Trinh, G. (n.d.). Direct-acting antiviral in the treatment of hepatitis c virus: a review of pharmacology and clinical application . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/242816

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Trinh, GiaKhanh. “Direct-acting antiviral in the treatment of hepatitis c virus: a review of pharmacology and clinical application .” Thesis, University of Debrecen. Accessed April 13, 2021. http://hdl.handle.net/2437/242816.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Trinh, GiaKhanh. “Direct-acting antiviral in the treatment of hepatitis c virus: a review of pharmacology and clinical application .” Web. 13 Apr 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Trinh G. Direct-acting antiviral in the treatment of hepatitis c virus: a review of pharmacology and clinical application . [Internet] [Thesis]. University of Debrecen; [cited 2021 Apr 13]. Available from: http://hdl.handle.net/2437/242816.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Trinh G. Direct-acting antiviral in the treatment of hepatitis c virus: a review of pharmacology and clinical application . [Thesis]. University of Debrecen; Available from: http://hdl.handle.net/2437/242816

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of Oxford

24. Howe, Jonathon David. Antiviral mechanisms of small molecules targeting the endoplasmic reticulum and Golgi apparatus.

Degree: PhD, 2014, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:04368b4b-2fd3-4fc7-8f89-ec39cd87e37d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658427

► N-linked glycosylation is the most common form of post-translational modification in nature and is essential to almost all enveloped viruses, including members of the Flaviviridae… (more)

▼ N-linked glycosylation is the most common form of post-translational modification in nature and is essential to almost all enveloped viruses, including members of the Flaviviridae family. The host cell N-linked glycoprotein processing pathway is utilised by these viruses and as such has long been identified as a potential target for the development of antiviral drugs. Here, the antiviral mechanisms of three classes of small molecules targeting the secretory pathway and altering viral envelope glycosylation are investigated, using the HCV surrogate model, BVDV. The antiviral activity of imino sugars, principally through α-glucosidase inhibition, is well-characterised and here, a group of novel adamantyl coupled imino sugars are investigated and demonstrated to inhibit ER α glucosidases, which correlates with their antiviral activity against BVDV. Additionally, BVDV is used to study the antiviral mechanism of action of nitazoxanide. Nitazoxanide, the parent compound of the thiazolide class of structures, is a broadly antimicrobial compound with antiviral activity against HBV, HCV, influenza, JEV and others. Here, nitazoxanide is shown to be antiviral against BVDV by inducing Ca²⁺ release from ATP-sensitive intracellular calcium stores, disrupting ER-Golgi trafficking and inhibiting complex glycan formation. Finally, the potential of Golgi endo-α-mannosidase as an antiviral target is explored, using the endomannosidase inhibitor glucose-isofagomine in conjunction with the imino sugar α-glucosidase inhibitor NAP-DNJ. Endomannosidase is shown to be a valid antiviral target for BVDV, both alone and in combination with α-glucosidase inhibition, and is utilised by viral glycoproteins to acquire complex glycan structure, even in the absence of α-glucosidase inhibition. Altogether, this work furthers our understanding of the varied antiviral mechanisms of small molecules targeting the secretory pathway, enhancing the search for novel antiviral drugs directed against host cell machinery.

Subjects/Keywords: 572; Biochemistry; Glycobiology; Glycosidase Inhibitors; Antiviral mechanisms

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APA (6^th Edition):

Howe, J. D. (2014). Antiviral mechanisms of small molecules targeting the endoplasmic reticulum and Golgi apparatus. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:04368b4b-2fd3-4fc7-8f89-ec39cd87e37d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658427

Chicago Manual of Style (16^th Edition):

Howe, Jonathon David. “Antiviral mechanisms of small molecules targeting the endoplasmic reticulum and Golgi apparatus.” 2014. Doctoral Dissertation, University of Oxford. Accessed April 13, 2021. http://ora.ox.ac.uk/objects/uuid:04368b4b-2fd3-4fc7-8f89-ec39cd87e37d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658427.

MLA Handbook (7^th Edition):

Howe, Jonathon David. “Antiviral mechanisms of small molecules targeting the endoplasmic reticulum and Golgi apparatus.” 2014. Web. 13 Apr 2021.

Vancouver:

Howe JD. Antiviral mechanisms of small molecules targeting the endoplasmic reticulum and Golgi apparatus. [Internet] [Doctoral dissertation]. University of Oxford; 2014. [cited 2021 Apr 13]. Available from: http://ora.ox.ac.uk/objects/uuid:04368b4b-2fd3-4fc7-8f89-ec39cd87e37d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658427.

Council of Science Editors:

Howe JD. Antiviral mechanisms of small molecules targeting the endoplasmic reticulum and Golgi apparatus. [Doctoral Dissertation]. University of Oxford; 2014. Available from: http://ora.ox.ac.uk/objects/uuid:04368b4b-2fd3-4fc7-8f89-ec39cd87e37d ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.658427

George Mason University

25. Voss, Kelsey. Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication .

Degree: 2014, George Mason University

URL: http://hdl.handle.net/1920/9093

► New World alphaviruses belonging to the family Togaviridae are known to infect humans and equines and cause encephalitic disease. The New World alphaviruses are classified… (more)

Subjects/Keywords: alphaviruses; host kinase; ERK; MAPK signalling; antiviral

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APA (6^th Edition):

Voss, K. (2014). Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication . (Thesis). George Mason University. Retrieved from http://hdl.handle.net/1920/9093

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):

Voss, Kelsey. “Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication .” 2014. Thesis, George Mason University. Accessed April 13, 2021. http://hdl.handle.net/1920/9093.

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

MLA Handbook (7^th Edition):

Voss, Kelsey. “Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication .” 2014. Web. 13 Apr 2021.

Vancouver:

Voss K. Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication . [Internet] [Thesis]. George Mason University; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/1920/9093.

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

Council of Science Editors:

Voss K. Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication . [Thesis]. George Mason University; 2014. Available from: http://hdl.handle.net/1920/9093

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

University of Washington

26. Koday, Merika Treants. Influenza vaccines and antivirals that target the conserved hemagglutinin stem.

Degree: PhD, 2016, University of Washington

URL: http://hdl.handle.net/1773/35616

► Influenza is a major public health threat, and pandemics, such as the 2009 H1N1 outbreak, are inevitable. Due to low efficacy of seasonal flu vaccines… (more)

▼ Influenza is a major public health threat, and pandemics, such as the 2009 H1N1 outbreak, are inevitable. Due to low efficacy of seasonal flu vaccines and the increase in drug-resistant strains of influenza viruses, there is a crucial need to develop new antivirals and vaccines to protect from seasonal and pandemic influenza. Recently, several broadly neutralizing antibodies have been characterized that bind to a highly conserved site on the viral hemagglutinin (HA) stem region. These antibodies are protective against a wide range of diverse influenza viruses indicating that the HA stem may be an excellent target for vaccines and antivirals. This thesis describes the development of a novel antiviral that effectively targets the HA stem, examines the ability of a conventional HA-based vaccine to elicit stem-specific antibodies, and explores the potential of stem-based vaccines to induce broadly neutralizing antibodies. Here I show that a small engineered protein computationally designed to bind to the same region of the HA stem as broadly neutralizing antibodies mediated protection against diverse strains of influenza in mice by a distinct mechanism that is independent of a host immune response. Since an antiviral targeting the conserved stem results in broad protection, I next investigated immunogenicity and protective efficacy of an E. coli heat-labile enterotoxin (LT) adjuvanted multigenic (LT-MA) universal influenza DNA vaccine consisting of four HA antigens, nucleoprotein (NP), and the ectodomain of the matrix protein (M2e) in nonhuman primates. Though the LT-MA DNA vaccine induced robust serum and mucosal antibody responses, it failed to induce broadly neutralizing antibodies. These results demonstrate that vaccination with full-length HA immunogen does not elicit stem-specific broadly neutralizing antibodies and further advancements in immunogen design are needed. In order to overcome this hurdle, I investigated a computationally designed DNA vaccine, based on the conserved HA stem, for the ability to induce antibody and T cell responses that provide protection from lethal influenza infection. Although these computationally designed headless HA immunogens were immunogenic and provided protection in vivo, they failed to elicit neutralizing antibodies. My results highlight the need for a vaccine immunogen that limits the immune response to the immunodominant head while directing the immune response to the stem and demonstrate that future vaccines will need to maintain the structural integrity of the fusion region in order to be successful. Together, these results have significant implications for the use of computational modeling to design new antivirals and vaccines against influenza and other viral diseases. Advisors/Committee Members: Fuller, Deborah H (advisor).

Subjects/Keywords: Antiviral; Influenza; Vaccine; Virology; Microbiology; Immunology; microbiology

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APA (6^th Edition):

Koday, M. T. (2016). Influenza vaccines and antivirals that target the conserved hemagglutinin stem. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/35616

Chicago Manual of Style (16^th Edition):

Koday, Merika Treants. “Influenza vaccines and antivirals that target the conserved hemagglutinin stem.” 2016. Doctoral Dissertation, University of Washington. Accessed April 13, 2021. http://hdl.handle.net/1773/35616.

MLA Handbook (7^th Edition):

Koday, Merika Treants. “Influenza vaccines and antivirals that target the conserved hemagglutinin stem.” 2016. Web. 13 Apr 2021.

Vancouver:

Koday MT. Influenza vaccines and antivirals that target the conserved hemagglutinin stem. [Internet] [Doctoral dissertation]. University of Washington; 2016. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/1773/35616.

Council of Science Editors:

Koday MT. Influenza vaccines and antivirals that target the conserved hemagglutinin stem. [Doctoral Dissertation]. University of Washington; 2016. Available from: http://hdl.handle.net/1773/35616

University of Minnesota

27. Greggs, Willie. Studies of feline leukemia virus drug susceptibility and antiviral mechanism of action.

Degree: PhD, Comparative and Molecular Biosciences, 2013, University of Minnesota

URL: http://hdl.handle.net/11299/177163

► Antiretroviral drugs have saved and extended the lives of millions of individuals infected with human immunodeficiency virus type 1 (HIV-1). The major classes of anti-HIV-1… (more)

▼ Antiretroviral drugs have saved and extended the lives of millions of individuals infected with human immunodeficiency virus type 1 (HIV-1). The major classes of anti-HIV-1 drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors and entry/fusion inhibitors. While antiretroviral drug regimens are commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of new antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of domesticated felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. The goal of this dissertation was to 1) determine the susceptibility of FeLV to drugs that could be amendable to clinical translation, and 2) explore the anti-FeLV mechanism of action of these drugs. FeLV was found to be susceptible to two anticancer drugs (i.e., decitabine and gemcitabine) as well as two anti-HIV-1 drugs (raltegravir and tenofovir). FeLV, but not HIV-1, was also found to be susceptible to cyclopentenyl cytosine. Mechanism of action studies suggested that decitabine and gemcitabine did not enhance FeLV mutagenesis, which is contrary to previous observations of enhanced HIV-1 mutagenesis observed with these drugs. Cyclopentenyl cytosine did not enhance viral mutagenesis, was observed to reduce dCTP levels in the Crandell-Rees feline kidney cell line, and FeLV susceptibility to cyclopentenyl cytosine was enhanced by a mutation in a conserved region of reverse transcriptase. These studies 1) support the further exploration of the clinical translation of decitabine, gemcitabine and cyclopentenyl cytosine for the treatment of FeLV infection, and 2) suggest differences in the antiviral mechanisms of action of decitabine, gemcitabine and cyclopentenyl cytosine between FeLV and HIV-1.

Subjects/Keywords: antiretroviral; antiviral; feline leukemia virus; mutagensis

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APA (6^th Edition):

Greggs, W. (2013). Studies of feline leukemia virus drug susceptibility and antiviral mechanism of action. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/177163

Chicago Manual of Style (16^th Edition):

Greggs, Willie. “Studies of feline leukemia virus drug susceptibility and antiviral mechanism of action.” 2013. Doctoral Dissertation, University of Minnesota. Accessed April 13, 2021. http://hdl.handle.net/11299/177163.

MLA Handbook (7^th Edition):

Greggs, Willie. “Studies of feline leukemia virus drug susceptibility and antiviral mechanism of action.” 2013. Web. 13 Apr 2021.

Vancouver:

Greggs W. Studies of feline leukemia virus drug susceptibility and antiviral mechanism of action. [Internet] [Doctoral dissertation]. University of Minnesota; 2013. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/11299/177163.

Council of Science Editors:

Greggs W. Studies of feline leukemia virus drug susceptibility and antiviral mechanism of action. [Doctoral Dissertation]. University of Minnesota; 2013. Available from: http://hdl.handle.net/11299/177163

Heriot-Watt University

28. Craven, David A. Synthesis of hydroxyalkylated pyrrolo- and thienopyrimidines as potential antiviral agents.

Degree: PhD, 1990, Heriot-Watt University

URL: http://hdl.handle.net/10399/911

Subjects/Keywords: 615.1; Antiviral chemotherapy

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APA (6^th Edition):

Craven, D. A. (1990). Synthesis of hydroxyalkylated pyrrolo- and thienopyrimidines as potential antiviral agents. (Doctoral Dissertation). Heriot-Watt University. Retrieved from http://hdl.handle.net/10399/911

Chicago Manual of Style (16^th Edition):

Craven, David A. “Synthesis of hydroxyalkylated pyrrolo- and thienopyrimidines as potential antiviral agents.” 1990. Doctoral Dissertation, Heriot-Watt University. Accessed April 13, 2021. http://hdl.handle.net/10399/911.

MLA Handbook (7^th Edition):

Craven, David A. “Synthesis of hydroxyalkylated pyrrolo- and thienopyrimidines as potential antiviral agents.” 1990. Web. 13 Apr 2021.

Vancouver:

Craven DA. Synthesis of hydroxyalkylated pyrrolo- and thienopyrimidines as potential antiviral agents. [Internet] [Doctoral dissertation]. Heriot-Watt University; 1990. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10399/911.

Council of Science Editors:

Craven DA. Synthesis of hydroxyalkylated pyrrolo- and thienopyrimidines as potential antiviral agents. [Doctoral Dissertation]. Heriot-Watt University; 1990. Available from: http://hdl.handle.net/10399/911

Kansas State University

29. Lang, Yuekun. Identification and evaluation of antivirals for Rift Valley fever virus.

Degree: PhD, Department of Diagnostic Medicine/Pathobiology, 2017, Kansas State University

URL: http://hdl.handle.net/2097/38195

► Rift Valley fever virus (RVFV) is an enveloped, negative-sense, ssRNA virus with a tripartite genome that causes morbidity and mortality in both livestock and humans.… (more)

▼ Rift Valley fever virus (RVFV) is an enveloped, negative-sense, ssRNA virus with a tripartite genome that causes morbidity and mortality in both livestock and humans. Although RVFV is mainly circulating in mainland Africa, this arthropod-borne virus is a potential threat to the other parts of the world. No fully licensed vaccines for human or animal use in the U.S., and effective antiviral drugs have not been identified. As virulent RVFV strains are only handled in biosafety level (BSL) 3 or higher level facilities in the U.S., few laboratories have access to RVFV which limits antiviral development. However, it is crucial to develop effective antivirals to protect public and animal health. Animal models that reproduce Rift Valley fever are vital to identifying and developing antiviral compounds. The currently available attenuated RVFV strain, MP12, provides a BSL-2 challenge model virus for preliminary investigations of RVFV prior to using the virulent RVFV strains. All strains of RVFV have a highly conserved genome, indicating that antivirals or vaccines effective against any RVFV strain will most likely be effective for all RVFV strains. Therefore, we hypothesize that the MP12 is a suitable model virus that can be used for identification and evaluation of effective RVF antivirals. The first objective of this project was to establish a mouse model susceptible to MP12 infection. Based on the literature, we selected and screened six different strains of mice to test their susceptibilities to MP12. We found the STAT-1 knockout mice are the most susceptible to MP12 infection based on clinical symptoms, mortality, viremia, virus replication, histopathological, and immunochemical analyses. Importantly, these mice displayed acute-onset hepatitis and delayed-onset encephalitis similar to severe cases of human RVFV infection. Our second objective was to identify potential antiviral drugs in vitro. We developed and employed a cell-based assay using the recombinant MP12 virus expressing Renilla luciferase to screen a library of 727 small compounds purchased from National Institutes of Health. Of the compounds, 23 were identified and further tested for their inhibitory activities on the recombinant MP12 virus expressing green fluorescent protein. Further plaque reduction assays confirmed that two compounds inhibited replication of parental RVFV MP12 strain with limited cytotoxic effects. The 50% inhibitory concentrations using an MP12 multiplicity of infection (MOI) of 2 were 211.4 µM and 139.5 µM, respectively. Our third objective was to evaluate these two candidates, 6-azauridine and mitoxantrone, in vivo using our mouse model. After one-hour post MP12 infection via an intranasal route, treatment was given intranasally twice daily. Mice treated with placebo and 6-azauridine displayed severe weight loss and reached the threshold for euthanasia with obvious neurological signs, while mice treated with ribavirin (a known antiviral drug) or mitoxantrone showed delayed onset of disease. This result indicates that the… Advisors/Committee Members: Wenjun Ma.

Subjects/Keywords: Rift Valley fever virus; Antiviral; Mouse model

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APA (6^th Edition):

Lang, Y. (2017). Identification and evaluation of antivirals for Rift Valley fever virus. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/38195

Chicago Manual of Style (16^th Edition):

Lang, Yuekun. “Identification and evaluation of antivirals for Rift Valley fever virus.” 2017. Doctoral Dissertation, Kansas State University. Accessed April 13, 2021. http://hdl.handle.net/2097/38195.

MLA Handbook (7^th Edition):

Lang, Yuekun. “Identification and evaluation of antivirals for Rift Valley fever virus.” 2017. Web. 13 Apr 2021.

Vancouver:

Lang Y. Identification and evaluation of antivirals for Rift Valley fever virus. [Internet] [Doctoral dissertation]. Kansas State University; 2017. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/2097/38195.

Council of Science Editors:

Lang Y. Identification and evaluation of antivirals for Rift Valley fever virus. [Doctoral Dissertation]. Kansas State University; 2017. Available from: http://hdl.handle.net/2097/38195

Loyola University Chicago

30. Novak, Jennifer Alexandra. Exosomes: Antiviral Agents in the Human Lung.

Degree: MS, Microbiology and Immunology, 2013, Loyola University Chicago

URL: https://ecommons.luc.edu/luc_theses/1467

► Hundreds of interferon effectors comprise the immediate host response to virus infection. One family of interferon stimulated genes is the IFITM (Interferon-Induced Transmembrane) proteins.… (more)

Subjects/Keywords: Antiviral; Exosome; IFITM; Interferon; Lung; Virology

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APA (6^th Edition):

Novak, J. A. (2013). Exosomes: Antiviral Agents in the Human Lung. (Thesis). Loyola University Chicago. Retrieved from https://ecommons.luc.edu/luc_theses/1467

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):

Novak, Jennifer Alexandra. “Exosomes: Antiviral Agents in the Human Lung.” 2013. Thesis, Loyola University Chicago. Accessed April 13, 2021. https://ecommons.luc.edu/luc_theses/1467.

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

MLA Handbook (7^th Edition):

Novak, Jennifer Alexandra. “Exosomes: Antiviral Agents in the Human Lung.” 2013. Web. 13 Apr 2021.

Vancouver:

Novak JA. Exosomes: Antiviral Agents in the Human Lung. [Internet] [Thesis]. Loyola University Chicago; 2013. [cited 2021 Apr 13]. Available from: https://ecommons.luc.edu/luc_theses/1467.

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

Council of Science Editors:

Novak JA. Exosomes: Antiviral Agents in the Human Lung. [Thesis]. Loyola University Chicago; 2013. Available from: https://ecommons.luc.edu/luc_theses/1467

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

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Open Access Theses and Dissertations