subject:(Antiviral Drugs)

Rhodes University

1. Magnus, Laura. Development, assessment and optimisation of oral famciclovir formulations for paediatric use.

Degree: Faculty of Pharmacy, Pharmacy, 2012, Rhodes University

URL: http://hdl.handle.net/10962/d1018244

► Many Active Pharmaceutical Ingredients (API) such as the antiviral agent famciclovir (FCV) are required for paediatric treatment but are not commercially available in age-appropriate dosage… (more)

▼ Many Active Pharmaceutical Ingredients (API) such as the antiviral agent famciclovir (FCV) are required for paediatric treatment but are not commercially available in age-appropriate dosage forms. It is common practice to prepare oral liquid dosage forms using commercially available tablets, capsules or powdered API and then dispersing or dissolving the crushed and/or powdered materials in a vehicle that the patient can swallow. Vehicles that are commonly used for this purpose include methylcellulose, syrup or combinations of these carriers where possible or commercially available suspending agents such as Ora-Sweet®, if available, can be used. However, several critical factors are overlooked when manufacturing extemporaneous formulations including, but not limited to, physical and chemical properties of the API, excipients, compatibility, stability and bioavailability issues. A stability-indicating High Performance Liquid Chromatography (HPLC) method for the analysis of FCV was developed and validated according to the International Conference on Harmonization (ICH) guidelines. The method is sensitive, selective, precise, accurate and linear over the concentration range 2-120 μg/ml. The stability of 25 mg/ml FCV formulations was assessed in vehicles manufactured from syrup simplex, hydroxypropyl methylcellulose (HPMC), Ora-Sweet® and an aqueous buffer (pH 6) following storage at 25 °C/60% RH and 40 °C/75% RH over six (6) to eight (8) weeks. The shelf life of the products was calculated as the longest period of storage for approximately 90% of the added FCV to be recovered. Formulations were manufactured using syrup simplex or HPMC with methylparaben and propylparaben individually or in combination and with sodium metabisulphite, ascorbic acid or citric acid as antioxidants. The resultant products were subject to quality control analysis for API content, viscosity, pH and appearance and the resultant data were subject to statistical analysis. The degradation rates were calculated for each product and a degradation profile plotted. The degradation rates of FCV in extemporaneous formulations were compared to those of FCV manufactured using a commercially available suspending agent and a buffered vehicle. FCV undergoes major degradation in the presence of sucrose, as observed for formulations in which the vehicle was syrup and Ora-Sweet®. FCV was found to be most stable when dissolved/dispersed in an HPMC vehicle incorporating sodium metabisulphite and a combination of parabens. The formulation that exhibited the maximum stability was manufactured using an aqueous solution buffered to pH 6. Due to the enhanced stability of FCV when added to a buffered vehicle a formulation in which an HPMC vehicle buffered to pH 6 with sodium metabisulphite, methylparaben and propylparaben was selected for optimisation using a Central Composite Design approach (CCD). In this way it was possible to establish a relationship between input variables such as pH, % w/v HPMC, % w/v antioxidant and % w/v preservative and the responses selected…

Subjects/Keywords: Drugs – Dosage forms; Drugs – Analysis; Capsules (Pharmacy); Antiviral agents; Pediatrics

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APA (6^th Edition):

Magnus, L. (2012). Development, assessment and optimisation of oral famciclovir formulations for paediatric use. (Thesis). Rhodes University. Retrieved from http://hdl.handle.net/10962/d1018244

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):

Magnus, Laura. “Development, assessment and optimisation of oral famciclovir formulations for paediatric use.” 2012. Thesis, Rhodes University. Accessed March 05, 2021. http://hdl.handle.net/10962/d1018244.

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

MLA Handbook (7^th Edition):

Magnus, Laura. “Development, assessment and optimisation of oral famciclovir formulations for paediatric use.” 2012. Web. 05 Mar 2021.

Vancouver:

Magnus L. Development, assessment and optimisation of oral famciclovir formulations for paediatric use. [Internet] [Thesis]. Rhodes University; 2012. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10962/d1018244.

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

Council of Science Editors:

Magnus L. Development, assessment and optimisation of oral famciclovir formulations for paediatric use. [Thesis]. Rhodes University; 2012. Available from: http://hdl.handle.net/10962/d1018244

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

Kyoto University / 京都大学

2. GHOSH, Gopal Chandra. Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition : 下水処理場での抗生物質と抗ウイルス剤の挙動とパンデミック発生時のその多様に伴うリスク.

Degree: 博士(工学), 2009, Kyoto University / 京都大学

URL: http://hdl.handle.net/2433/85391 ; http://dx.doi.org/10.14989/doctor.k14931

► The concern for pharmaceutically active compounds (PhACs) as contaminants in the environment and the need to assess their environmental risk have greatly increased since the… (more)

▼ The concern for pharmaceutically active compounds (PhACs) as contaminants in the environment and the need to assess their environmental risk have greatly increased since the early nineties. Among PhACs, antibiotics and antiviral drugs are of important concern due to their role in growing antibiotic and antiviral drugs resistance among pathogenic bacteria and influenza viruses, respectively. Besides resistance issue, the compounds may upset sensitive ecosystems as they are designed to be highly bioactive. Clinically-important antibiotics are virtually ubiquitous contaminants in sewage water and surface water. Notably, recent emergence of novel influenza and use of anti-influenza drugs (specially Tamiflu®) during seasonal influenza、 influenza epidemics and for future pandemic are of emerging concern. Every year seasonal influenza epidemic causes tens of millions of respiratory illnesses and 250, 000 to 500, 000 deaths worldwide. WHO (World Health Organization) recommend the use of antiviral drug Tamiflu® during pandemic, as they are easy to use. Currently only Japan uses over eighty percent of Tamiflu® prescribed globally during common seasonal influenza. It is a fact that a huge amount of antiviral drugs and antibiotics ( for post infection cure of respiratory illness) will be used during an influenza pandemic and will arrive to sewage treatment plants (STPs).Unfortunately, these compounds behaviors are mostly unknown in both conventional and advanced STPs. The exposure of antiviral drug in the wild fowl gut and its implications for hastening the generation of antiviral-resistance in avian influenza viruses are also an emerging issue. The major objective of this thesis work was to investigate the occurrence of antibiotics and antiviral drugs in sewage treatment plants and their fate in different sewage treatment plants. The specific objectives were as follows: (a) to established appropriate analytical method for the selected antibiotics and antiviral drugs in sewage treatment plants, (b) to investigate the occurrence and removal of antibiotics and antiviral drugs in sewage treatment plants differ in technology and operation conditions; and (c) to predicts environmental concentration of the target compounds during a pandemics and appraisal of appropriate technology to reduce the risk associated with widespread use under pandemic conditions. In this study we selected twenty antibiotics: one beta-lactam: ampicillin; four macrolides: azithromycin, clarithromycin and roxithromycin; five quinolones: ciprofloxacin, enrofloxacin, levofloxacin, nalidixic acid and norfloxacin; two tetracycline: tetracycline and oxytetracycline; five sulfonamides: sulfadimethoxine, sulfadimizine, sulfamerazine, sulfam- ethoxazole and sulfamonomethoxine; and four others: lincomycin, novobiocin, salinomycin and trimethoprim. Oseltamivir Carboxylate (OC), the active metabolite of oseltamivir phosphate (Tamiflu®) and amantadine (AMN) were selected as antiviral drugs. This dissertation consists of nine chapters: Chapter I describe the background and…

Subjects/Keywords: LC/MS/MS; Antibiotics; Antiviral Drugs; Sewage Treatment Plants; Pandemic Influenza

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APA (6^th Edition):

GHOSH, G. C. (2009). Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition : 下水処理場での抗生物質と抗ウイルス剤の挙動とパンデミック発生時のその多様に伴うリスク. (Thesis). Kyoto University / 京都大学. Retrieved from http://hdl.handle.net/2433/85391 ; http://dx.doi.org/10.14989/doctor.k14931

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):

GHOSH, Gopal Chandra. “Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition : 下水処理場での抗生物質と抗ウイルス剤の挙動とパンデミック発生時のその多様に伴うリスク.” 2009. Thesis, Kyoto University / 京都大学. Accessed March 05, 2021. http://hdl.handle.net/2433/85391 ; http://dx.doi.org/10.14989/doctor.k14931.

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

MLA Handbook (7^th Edition):

GHOSH, Gopal Chandra. “Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition : 下水処理場での抗生物質と抗ウイルス剤の挙動とパンデミック発生時のその多様に伴うリスク.” 2009. Web. 05 Mar 2021.

Vancouver:

GHOSH GC. Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition : 下水処理場での抗生物質と抗ウイルス剤の挙動とパンデミック発生時のその多様に伴うリスク. [Internet] [Thesis]. Kyoto University / 京都大学; 2009. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/2433/85391 ; http://dx.doi.org/10.14989/doctor.k14931.

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

Council of Science Editors:

GHOSH GC. Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition : 下水処理場での抗生物質と抗ウイルス剤の挙動とパンデミック発生時のその多様に伴うリスク. [Thesis]. Kyoto University / 京都大学; 2009. Available from: http://hdl.handle.net/2433/85391 ; http://dx.doi.org/10.14989/doctor.k14931

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

Stellenbosch University

3. Brigg, Siobhan Ernan. Lead optimisation of an indole based HIV-1 non-nucleoside reverse transcriptase inhibitor.

Degree: MSc, Chemistry and Polymer Science, 2017, Stellenbosch University

URL: http://hdl.handle.net/10019.1/102766

► ENGLISH ABSTRACT: HIV-1 remains the worst pandemic faced by mankind since its discovery as the causative agent of AIDS in the early 1980s. An enormous… (more)

▼ ENGLISH ABSTRACT: HIV-1 remains the worst pandemic faced by mankind since its discovery as the causative agent of AIDS in the early 1980s. An enormous amount of research has been done to find a cure, but to date there has been no success and resistance is widespread among the available treatment. This project focused on the development of novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) using a rational design approach. The lead compound, ethyl 5-chloro-3-(methoxy(phenyl)methyl)-1H-indole-2-carboxylate, was shown to have low nano-molar potency against HIV-1 (IC50 = 16 nM), however it had two main shortcomings which needed to be addressed; poor resistance profile and poor acid stability. Previous research had shown the resistance profile could be improved by introducing meta substitution on the phenyl moiety which interacts with Tyr181 of the NNRTI binding pocket (NNIBP). We were successful in synthesising several meta substituted phenyl derivatives of the lead compound and these were shown to be equally as potent as the lead compound. Their activity against resistant strains is yet to be determined as we are awaiting the results from biological testing. The presence of an acid labile methyl ether functionality on the molecule which was susceptible to an acid catalysed indole mediated SN1 substitution in aqueous acidic medium meant that the lead compound could never be considered as a candidate for an orally available drug. The methyl ether moiety was exchanged for a sulfide moiety and several of these derivatives were successfully synthesised. Acid stability tests showed that we were successful in our endeavour to improve the acid stability, offering an advantage over the lead compound despite a slight reduction in potency. However to completely eliminate the possibility of substitution, we replaced the methyl ether moiety for an ethyl group, successfully synthesising ethyl 5-chloro-3-(1-phenylpropyl)-1H-indole-2-carboxylate and 5-chloro-3-(1-phenylpropyl)-1H-indole-2-carboxamide and we are currently awaiting the results from biological testing to determine whether this derivative is active against HIV-1. The functionality in the 2-position of the indole was also investigated through the synthesis of 5-chloro-3-(methoxy(phenyl)methyl)-1H-indole and 5-chloro-3-((methylthio)(phenyl)methyl)-1H-indole. These derivatives lacking a group in the 2-position of the indole showed significant reduction in potency. Replacement of the ethyl ester for an isobutyl ester to give isobutyl 5-chloro-3-((3,5-dimethylphenyl)(methylthio)methyl)-1H-indole-2-carboxylate, showed some maintenance of potency, however the larger side chain was not well accommodated in the NNIBP. The presence of a chiral centre on the lead compound, and all derivatives synthesised in the project, resulted in our final aim; we set out to develop a method for resolving these enantiomers. Unfortunately, although we employed a variety of different strategies, including the use of chiral auxiliaries and the classical resolution method of attempting to… Advisors/Committee Members: Pelly, Stephen, C., Blackie, Margeret, A. L., Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science..

Subjects/Keywords: HIV infections; NNRTI; Synthetic drugs; UCTD; Antiviral nucleosides

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

APA (6^th Edition):

Brigg, S. E. (2017). Lead optimisation of an indole based HIV-1 non-nucleoside reverse transcriptase inhibitor. (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/102766

Chicago Manual of Style (16^th Edition):

Brigg, Siobhan Ernan. “Lead optimisation of an indole based HIV-1 non-nucleoside reverse transcriptase inhibitor.” 2017. Masters Thesis, Stellenbosch University. Accessed March 05, 2021. http://hdl.handle.net/10019.1/102766.

MLA Handbook (7^th Edition):

Brigg, Siobhan Ernan. “Lead optimisation of an indole based HIV-1 non-nucleoside reverse transcriptase inhibitor.” 2017. Web. 05 Mar 2021.

Vancouver:

Brigg SE. Lead optimisation of an indole based HIV-1 non-nucleoside reverse transcriptase inhibitor. [Internet] [Masters thesis]. Stellenbosch University; 2017. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10019.1/102766.

Council of Science Editors:

Brigg SE. Lead optimisation of an indole based HIV-1 non-nucleoside reverse transcriptase inhibitor. [Masters Thesis]. Stellenbosch University; 2017. Available from: http://hdl.handle.net/10019.1/102766

University of St. Andrews

4. Rodrigues, Ana Mara Lopes. Interferon, virus vaccines and antiviral drugs .

Degree: 2008, University of St. Andrews

URL: http://hdl.handle.net/10023/428

► The emergence of viruses with zoonotic potential, i.e. with the potential ability to cross species barriers to infect unnatural hosts, poses a huge threat to… (more)

▼ The emergence of viruses with zoonotic potential, i.e. with the potential ability to cross species barriers to infect unnatural hosts, poses a huge threat to humans. It is therefore essential to develop new methodologies to rapidly and efficiently generate attenuated virus vaccine candidates to attempt to control the threat. Viruses need to be able to at least partially inhibit the host’s innate defence mechanism, known as the interferon (IFN) system, to replicate efficiently in vivo and establish a productive infection. It has been previously reported that viruses that have lost their ability to circumvent the host’s IFN response, or IFN-sensitive viruses, are promising candidates for live attenuated virus vaccines. Here we report on the development of a cell-based method to attempt to rapidly select IFN-sensitive viruses that can not block IFN signalling, from wild-type virus populations. Lentivirus vectors containing selection markers (HSV-tk – Herpes Simplex virus thymidine kinase gene and pac – puromycin resistance gene) under the control of a tight IFN-inducible promoter (the murine Mx1 promoter) were generated and used to specifically engineer HEp2 cell lines, termed Mx GIPSE and Mx TIPSE, for this purpose. The developed methodology relies on the engineered cell lines and a selection procedure using exogenous IFN-α and puromycin: if a cell is infected with IFN-resistant virus, it will die in the presence of IFN-α and puromycin because IFN signalling will be blocked, thereby blocking the activation of the Mx1 promoter and consequent expression of pac; if a cell is infected with an IFN-sensitive virus, it will survive in the presence of IFN-α and puromycin because the Mx1 promoter will become activated through the IFN signalling pathway, leading to the expression of pac. IFN-sensitive viruses can then be rescued from the surviving cells, and amplified using IFN-permissive cell lines expressing viral IFN antagonist proteins (proteins that block the host’s IFN response). When tested on PIV5 strains CPI- (an IFN-sensitive virus) and CPI+ (an IFN-resistant virus), the developed method allowed the survival and amplification of cells infected with CPI-, whilst cell death was observed for cells infected with CPI+. Whilst the developed methodology seems promising, further developments of the system are required. The possibilities of using the developed methodology in combination with other techniques, such as FACS sorting and immune selection, to rapidly select IFN-sensitive mutant viruses from wild-type and mutagenised virus populations are discussed. The potential to use Mx TIPSE cells to select IFN-resistant revertant viruses from IFN-sensitive virus populations is also discussed. In addition, a high throughput screening assay has been developed using the engineered Mx GIPSE and Mx TIPSE cell lines to search for compounds that block IFN signalling or that block the action of viral IFN antagonist proteins. Compounds that block IFN signalling would potentially be useful as anti-inflammatory… Advisors/Committee Members: Randall, R. E (advisor).

Subjects/Keywords: Interferon; Virus vaccines; Antiviral drugs

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

APA (6^th Edition):

Rodrigues, A. M. L. (2008). Interferon, virus vaccines and antiviral drugs . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/428

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):

Rodrigues, Ana Mara Lopes. “Interferon, virus vaccines and antiviral drugs .” 2008. Thesis, University of St. Andrews. Accessed March 05, 2021. http://hdl.handle.net/10023/428.

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

MLA Handbook (7^th Edition):

Rodrigues, Ana Mara Lopes. “Interferon, virus vaccines and antiviral drugs .” 2008. Web. 05 Mar 2021.

Vancouver:

Rodrigues AML. Interferon, virus vaccines and antiviral drugs . [Internet] [Thesis]. University of St. Andrews; 2008. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10023/428.

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

Council of Science Editors:

Rodrigues AML. Interferon, virus vaccines and antiviral drugs . [Thesis]. University of St. Andrews; 2008. Available from: http://hdl.handle.net/10023/428

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

Heriot-Watt University

5. Harrison, M. Synthesis of acyclic c-nucleosides as potential antiviral agents.

Degree: PhD, 1988, Heriot-Watt University

URL: http://hdl.handle.net/10399/1004

Subjects/Keywords: 615.1; Synthesis of antiviral drugs

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

APA (6^th Edition):

Harrison, M. (1988). Synthesis of acyclic c-nucleosides as potential antiviral agents. (Doctoral Dissertation). Heriot-Watt University. Retrieved from http://hdl.handle.net/10399/1004

Chicago Manual of Style (16^th Edition):

Harrison, M. “Synthesis of acyclic c-nucleosides as potential antiviral agents.” 1988. Doctoral Dissertation, Heriot-Watt University. Accessed March 05, 2021. http://hdl.handle.net/10399/1004.

MLA Handbook (7^th Edition):

Harrison, M. “Synthesis of acyclic c-nucleosides as potential antiviral agents.” 1988. Web. 05 Mar 2021.

Vancouver:

Harrison M. Synthesis of acyclic c-nucleosides as potential antiviral agents. [Internet] [Doctoral dissertation]. Heriot-Watt University; 1988. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10399/1004.

Council of Science Editors:

Harrison M. Synthesis of acyclic c-nucleosides as potential antiviral agents. [Doctoral Dissertation]. Heriot-Watt University; 1988. Available from: http://hdl.handle.net/10399/1004

University of Canterbury

6. Somasundaram, Balaji. A surface plasmon resonance assay to determine the effect of influenza neuraminidase mutations on its affinity with antiviral drugs.

Degree: PhD, Chemical Engineering, 2013, University of Canterbury

URL: http://dx.doi.org/10.26021/3424

► The outbreak of pandemic influenza and its ability to spread rapidly makes it a severe threat to public health. Antiviral drugs such as oseltamivir (Roche’s… (more)

▼ The outbreak of pandemic influenza and its ability to spread rapidly makes it a severe threat to public health. Antiviral drugs such as oseltamivir (Roche’s Tamiflu™) and zanamivir (GlaxoSmithKline’s Relenza™) are neuraminidase (NA) inhibitors (NI), which bind more tightly to NA than its natural substrate, sialic acid. However, the virus can acquire resistance to antiviral drugs by developing single point mutations (such as H274Y) in the target protein. Thus in some cases the drugs may not be as effective as expected. The high level of inconsistency exhibited by fluorometric assays and the short half-life of the chemiluminescent assay for monitoring drug resistance lead to the need for a simple, label-free, reliable assay. To address this problem, this work focused on three main objectives: 1) to determine the binding affinities of two common anti-viral drugs (oseltamivir and zanamivir) against the influenza NA wild type and drug resistant mutants using bioinformatics software Schrodinger Suite™ 2010. 2) To develop a reliable label-free, real-time, surface plasmon resonance (SPR) assay to measure the binding affinity between influenza viral coat protein neuraminidase (wild type and mutant) and anti-viral drugs. 3) To develop an SPR inhibition assay to quantitatively compare the interactions of sialic acid, zanamivir and oseltamivir with the viral coat protein neuraminidase (wild type and mutant). The entire docking process was carried out using Schrödinger Suite™ 2010. The 2009 pandemic H1N1 neuraminidase (PDB: 3NSS) was used throughout the docking studies as the wild type structure. Five mutants (H274Y, N294S, H274N, A346N and I222V) and three ligands (sialic acid, oseltamivir and zanamivir) were built using the maestro module. The grid-based ligand docking with energetics (GLIDE) module and induced fit docking (IFD) module were used for docking studies. The binding affinities, Gibbs free energy change (∆G) and molecular mechanics-generalized born energy/ solvent accessible area (MM-GB/SA) values for wild-type NA interactions show that both the antiviral drugs studied interact strongly with the wild-type protein. The ∆G values for all antiviral interactions with mutant NA forms were reduced in magnitude, thereby indicating that they are less favourable than interactions with the wild-type protein. A similar trend was observed with MM-GB/SA results. Amongst all of the computed values, MM-GB/SA was the closest to the experimental data. In several cases, the interactions between the anti-viral drugs and NA mutants were markedly less favourable than those between sialic acid and the same mutants, indicating that these mutations could confer anti-viral resistance. Influenza NA wild-type and H274Y mutant were expressed in baculovirus expression system (BVES) in insect cells. The expressed proteins were partially purified using the standard purification techniques of anion exchange and size exclusion chromatography (SEC). A fluorometric activity assay was performed on the recombinant proteins. Both the wild type…

Subjects/Keywords: Surface plasmon resonance; Influenza neuraminidase; Binding affinity; Antiviral drugs; Zanamivir; Drug resistance.

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

APA (6^th Edition):

Somasundaram, B. (2013). A surface plasmon resonance assay to determine the effect of influenza neuraminidase mutations on its affinity with antiviral drugs. (Doctoral Dissertation). University of Canterbury. Retrieved from http://dx.doi.org/10.26021/3424

Chicago Manual of Style (16^th Edition):

Somasundaram, Balaji. “A surface plasmon resonance assay to determine the effect of influenza neuraminidase mutations on its affinity with antiviral drugs.” 2013. Doctoral Dissertation, University of Canterbury. Accessed March 05, 2021. http://dx.doi.org/10.26021/3424.

MLA Handbook (7^th Edition):

Somasundaram, Balaji. “A surface plasmon resonance assay to determine the effect of influenza neuraminidase mutations on its affinity with antiviral drugs.” 2013. Web. 05 Mar 2021.

Vancouver:

Somasundaram B. A surface plasmon resonance assay to determine the effect of influenza neuraminidase mutations on its affinity with antiviral drugs. [Internet] [Doctoral dissertation]. University of Canterbury; 2013. [cited 2021 Mar 05]. Available from: http://dx.doi.org/10.26021/3424.

Council of Science Editors:

Somasundaram B. A surface plasmon resonance assay to determine the effect of influenza neuraminidase mutations on its affinity with antiviral drugs. [Doctoral Dissertation]. University of Canterbury; 2013. Available from: http://dx.doi.org/10.26021/3424

University of Gothenburg / Göteborgs Universitet

7. Bergefall, Kicki 1975-. Interaction of herpes simplex virus with cell surface glycosaminoglycans as a target for antiviral intervention.

Degree: 2005, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/16606

► Herpes simplex virus (HSV) infections in humans are predominantly manifested as oral cold sores or genital ulcers. As HSV infects cells by interaction with cell… (more)

▼ Herpes simplex virus (HSV) infections in humans are predominantly manifested as oral cold sores or genital ulcers. As HSV infects cells by interaction with cell surface heparan sulfate (HS) and/or chondroitin sulfate (CS), the aim of the research work presented in this thesis was to explore the possibility of antiviral intervention with compounds that mimic HS or CS. Three structurally distinct compounds were found to target this step of HSV-cell interaction thus preventing the HSV infection of cells. These include (i) the low molecular weight HS-mimetic PI-88, (ii) CS type E (CS-E) derived from squid cartilage, and (iii) the monosulfated cyclitol SC1. PI-88 is a mixture of highly sulfated mannose-containing di- to hexa-saccharides that was previously explored as an anti-cancer drug. In this thesis PI-88 was found to be a potent inhibitor of the cell-to-cell spread of HSV. This feature of the virus is essential for the development of both viral plaques in cell cultures and of oral or genital lesions in humans. One structural feature of PI-88, its low molecular weight, was found to be important for the antiviral properties as PI-88 but not the high molecular weight HS-mimetic heparin could inhibit the cell-to-cell spread of HSV. The antiviral activity of PI-88 is very likely due to its ability to access the narrow intercellular space where PI-88 was demonstrated to block the interaction of viral envelope glycoproteins gB, gC, and gD with cellular HS.Although cell surface CS is regarded as an auxiliary receptor for HSV and purified preparations of CS types A, B, and C are known to be poor inhibitors of HSV invasion of cells, in this thesis it was found that CS type E, from squid cartilage, was one of the most potent inhibitors of initial virus adherence to cultured cells. The concentrations of CS-E that inhibited the virus infectivity by 50% (IC50) were approximately 0.1 µg/ml in normal cells, and <1 ng/ml in mutant CS-expressing cells. In addition, because disaccharide analysis of CS forms found on the cell surface revealed the presence of E disaccharide units, CS-E may block HSV invasion of cells by interference with the virus binding to the E unit of the cell surface CS.By screening for the anti-HSV activity of a mini-library of 96 compounds, previously synthesized to search for inhibitors of protein-HS interaction, a monosulfated cyclitol molecule designated SC1 was discovered to completely inhibit HSV infectivity in cultured cells. SC1 was found to target and to inactivate the viral particle. Complete inactivation of HSV type 1 and type 2 particles occurred within 5 min at 37°C and 15 30 min at 37°C respectively. In addition SC1, in contrast to some other virus-inactivating agents, exhibited substantial selectivity in its antiviral action as the concentration of SC1 that was toxic for cells was at least fifty fold higher than the virus-inactivating doses. The anti-HSV activity of SC1 was found to be due to the inactivation of viral components other than those required for the virus attachment to cells.In…

Subjects/Keywords: HSV; glycoproteins; glycosaminoglycans; virus receptor; antiviral drugs

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APA (6^th Edition):

Bergefall, K. 1. (2005). Interaction of herpes simplex virus with cell surface glycosaminoglycans as a target for antiviral intervention. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/16606

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):

Bergefall, Kicki 1975-. “Interaction of herpes simplex virus with cell surface glycosaminoglycans as a target for antiviral intervention.” 2005. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed March 05, 2021. http://hdl.handle.net/2077/16606.

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

MLA Handbook (7^th Edition):

Bergefall, Kicki 1975-. “Interaction of herpes simplex virus with cell surface glycosaminoglycans as a target for antiviral intervention.” 2005. Web. 05 Mar 2021.

Vancouver:

Bergefall K1. Interaction of herpes simplex virus with cell surface glycosaminoglycans as a target for antiviral intervention. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2005. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/2077/16606.

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

Council of Science Editors:

Bergefall K1. Interaction of herpes simplex virus with cell surface glycosaminoglycans as a target for antiviral intervention. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2005. Available from: http://hdl.handle.net/2077/16606

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

University of Georgia

8. Blue, Shawn Kendale. Pharmacokinetics of anti-HIV agents in rodents.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/26575

► The treatment of HIV/AIDS is one of, if not, the most challenging medical enigmas of the 20th and 21st centuries. At the time of its… (more)

▼ The treatment of HIV/AIDS is one of, if not, the most challenging medical enigmas of the 20th and 21st centuries. At the time of its discovery, HIV patients were predominantly homosexual White males in America. The demographics have changed drastically over the past two decades. Now women make up nearly 50% of global HIV/AIDS patients. The current feminization of HIV demographics has led to another obstacle, mother to child transmission (MTCT). These statistics, coupled with the fact that vertical transmission is the largest factor in the number of newly diagnosed juvenile HIV/AIDS patients, create a need to optimize treatment of HIV positive pregnant women, to reduce vertical transmission of HIV. It has been shown that administration of anti-HIV medications during pregnancy, delivery and to the infant after birth greatly reduces the risk of vertical transmission. Understanding the pharmacokinetics of HIV/AIDS medications alone and in combination during pregnancy is necessary in the development of more effective methods of vertical transmission prophylaxis. Using a pregnant rat model, we have developed analytical methods and investigated the pharmacokinetics and placental transport of anti-HIV drugs alone and in combination. These studies allowed us to determine and understand any possible interactions between drugs in combination. Studies were performed on timed-pregnant Sprague-Dawley rats and pharmacokinetic analysis was performed using WinNonlin. While current methods of treating HIV/AIDS patients have been highly successful, the chance of viral mutations and resistance to Anti-Retroviral Therapy often occurs. In order to combat the resistance of reverse transcriptase inhibitors (NRTI and NNRTI) and protease inhibitors, scientists have continually searched for additional targets on HIV. For instance, integrase inhibitors, block the action of integrase, a viral enzyme, which integrates HIV DNA into the target cells. We have determined the pharmacokinetic profile of an investigational integrase inhibitor. In vivo animal studies were being performed on male Sprague-Dawley rats and female PXR-KO and hPXR transgenic mice and pharmacokinetic analysis was performed using WinNonlin.

Subjects/Keywords: HIV; Pharmacokinetics; Stavudine; Lamivudine; D4T; DDC; Placental Transport; NRTI; Nucleoside Reverse Transcriptase Inhibitors; HPLC; Antiviral Drugs; Integrase Inhibitors

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❌

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

APA (6^th Edition):

Blue, S. K. (2014). Pharmacokinetics of anti-HIV agents in rodents. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/26575

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):

Blue, Shawn Kendale. “Pharmacokinetics of anti-HIV agents in rodents.” 2014. Thesis, University of Georgia. Accessed March 05, 2021. http://hdl.handle.net/10724/26575.

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

MLA Handbook (7^th Edition):

Blue, Shawn Kendale. “Pharmacokinetics of anti-HIV agents in rodents.” 2014. Web. 05 Mar 2021.

Vancouver:

Blue SK. Pharmacokinetics of anti-HIV agents in rodents. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10724/26575.

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

Council of Science Editors:

Blue SK. Pharmacokinetics of anti-HIV agents in rodents. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/26575

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

Utah State University

9. Okleberry, Kevin M. Metabolism of Selected Antiviral Agents in Cells Infected with Drug-Resistant and Wild-Type Strains of Murine Cytomegalovirus.

Degree: MS, Animal, Dairy, and Veterinary Sciences, 1995, Utah State University

URL: https://digitalcommons.usu.edu/etd/4657

► Resistance of human viral pathogens to various antiviral drugs is a serious medical problem. Two modes of drug resistance in cytomegalovirus infections have been… (more)

▼ Resistance of human viral pathogens to various antiviral drugs is a serious medical problem. Two modes of drug resistance in cytomegalovirus infections have been observed, the first being altered (decreased) drug metabolism by the infected cells, and the second reduced sensitivity of the viral deoxyribonucleic acid polymerase enzyme to the active form of the drug. Mice infected with the murine cytomegalovirus have been used extensively as an animal model for the human cytomegalovirus, and drug-resistant strains in this model have been identified. To better understand the mode of drug resistance of the virus, the metabolism of two antiviral drugs, 9-(1,3-dihydroxy-2-propoxymethyl)guanine (ganciclovir) and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (cidofovir), was studied in cells infected with the virus. The degree of resistance of the mutant virus strain to these two drugs and also to the drug phosphonoformic acid (foscarnet) was measured in viral plaque reduction assays. The resistant strain was 14-,4-, and 11-fold less sensitive to the drugs ganciclovir, foscarnet, and cidofovir, respectively, than a sensitive (wildtype) strain Metabolism of the antiviral drugs ganciclovir and cidofovir was studied in C127I mouse mammary tumor cells infected with the mutant strain. Uninfected C127I cells and C127I cells infected with the sensitive strain of murine cytomegalovirus were used as controls. The cells were treated with tritium-labeled ganciclovir or cidofovir and studied under a variety of parameters. Among these were duration of treatment, multiplicity of infection, and concentration of compound. After incubating, the cells were acid extracted and analyzed with high-pressure liquid chromatography. The radioactivity of each sample was measured on a scintillation counter and converted into picomoles of drug per million cells. No significant difference was observed between the virus strains in terms of metabolism or catabolism of the two drugs. This effect remained constant, even when controlling for parameters such as the amount of virus infecting each cell, duration of treatment, or concentration of drug. Based on these results, it appears that the mode of resistance in this mutant strain of virus to ganciclovir and cidofovir is not due to an alteration in metabolism of these two compounds by infected cells. Thus, it is proposed that drug resistance in this mutant strain of virus is due to altered viral deoxyribonucleic acid polymerase function. Advisors/Committee Members: Reed P. Warren, ;.

Subjects/Keywords: resistance; viral pathogens; antiviral drugs; infections; Toxicology

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❌

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

APA (6^th Edition):

Okleberry, K. M. (1995). Metabolism of Selected Antiviral Agents in Cells Infected with Drug-Resistant and Wild-Type Strains of Murine Cytomegalovirus. (Masters Thesis). Utah State University. Retrieved from https://digitalcommons.usu.edu/etd/4657

Chicago Manual of Style (16^th Edition):

Okleberry, Kevin M. “Metabolism of Selected Antiviral Agents in Cells Infected with Drug-Resistant and Wild-Type Strains of Murine Cytomegalovirus.” 1995. Masters Thesis, Utah State University. Accessed March 05, 2021. https://digitalcommons.usu.edu/etd/4657.

MLA Handbook (7^th Edition):

Okleberry, Kevin M. “Metabolism of Selected Antiviral Agents in Cells Infected with Drug-Resistant and Wild-Type Strains of Murine Cytomegalovirus.” 1995. Web. 05 Mar 2021.

Vancouver:

Okleberry KM. Metabolism of Selected Antiviral Agents in Cells Infected with Drug-Resistant and Wild-Type Strains of Murine Cytomegalovirus. [Internet] [Masters thesis]. Utah State University; 1995. [cited 2021 Mar 05]. Available from: https://digitalcommons.usu.edu/etd/4657.

Council of Science Editors:

Okleberry KM. Metabolism of Selected Antiviral Agents in Cells Infected with Drug-Resistant and Wild-Type Strains of Murine Cytomegalovirus. [Masters Thesis]. Utah State University; 1995. Available from: https://digitalcommons.usu.edu/etd/4657

Georgia Tech

10. Hagos, Asmerom M. Tricyclic purine analogues as antiparasitic and antiviral agents.

Degree: PhD, Chemistry and Biochemistry, 2003, Georgia Tech

URL: http://hdl.handle.net/1853/5319

Subjects/Keywords: Purines Synthesis; Antiviral agents; Antiparasitic agents; Trypanosoma brucei; Drugs Design; Trypanosoma brucei; Purines Synthesis; Drugs Design; Antiviral agents; Antiparasitic agents

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

APA (6^th Edition):

Hagos, A. M. (2003). Tricyclic purine analogues as antiparasitic and antiviral agents. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/5319

Chicago Manual of Style (16^th Edition):

Hagos, Asmerom M. “Tricyclic purine analogues as antiparasitic and antiviral agents.” 2003. Doctoral Dissertation, Georgia Tech. Accessed March 05, 2021. http://hdl.handle.net/1853/5319.

MLA Handbook (7^th Edition):

Hagos, Asmerom M. “Tricyclic purine analogues as antiparasitic and antiviral agents.” 2003. Web. 05 Mar 2021.

Vancouver:

Hagos AM. Tricyclic purine analogues as antiparasitic and antiviral agents. [Internet] [Doctoral dissertation]. Georgia Tech; 2003. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/1853/5319.

Council of Science Editors:

Hagos AM. Tricyclic purine analogues as antiparasitic and antiviral agents. [Doctoral Dissertation]. Georgia Tech; 2003. Available from: http://hdl.handle.net/1853/5319

11. Ferreira, Daniela Filipa Santos. Análogos de nucleósidos com atividade antiviral.

Degree: 2017, Universidade Fernando Pessoa

URL: https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/6567

►

Os vírus são agentes infeciosos de pequenas dimensões. Não possuem metabolismo próprio e são considerados parasitas intracelulares obrigatórios, pois precisam de um hospedeiro para se… (more)

▼

Os vírus são agentes infeciosos de pequenas dimensões. Não possuem metabolismo próprio e são considerados parasitas intracelulares obrigatórios, pois precisam de um hospedeiro para se reproduzir. A quimioterapia antiviral foi uma área praticamente inexplorada até meados do século XX. As infeções provocadas pelo vírus herpes simplex (HSV-1) e a descoberta do vírus da imunodeficiência humana (HIV) revelaram ser a principal alavanca para o desenvolvimento de moléculas com atividade antiviral. As infeções virais são difíceis de tratar, porque os vírus partilham muitos dos processos metabólicos da célula hospedeira, sendo difícil encontrar fármacos com uma toxicidade seletiva e que atuem apenas no vírus. No entanto, existem algumas enzimas que são específicas de determinados vírus, permitindo o desenvolvimento de antivirais que atuam por inibição de determinadas enzimas virais, apresentando assim uma menor toxicidade para o hospedeiro. A maioria dos antivirais usados hoje em dia, são análogos de nucleósidos, desde os mais antigos, como o aciclovir (que tem como alvo a DNA polimerase), até aos mais recentes, como o sofosbuvir (que tem como alvo a RNA polimerase). De modo a alcançar uma melhor biodisponibilidade oral e/ou diminuir a toxicidade para o hospedeiro, tem-se apostado no desenvolvimento de pró-fármacos clássicos.

Viruses are small infectious agents. They don´t have their own metabolism and are considered as obligate intracellular parasites, since they need a host to reproduce. Antiviral chemotherapy constituted a practically unexplored area until the midle of the 20th century. Infections caused by the herpes simplex virus (HSV-1) and the discovery of the human immunodeficiency virus (HIV) promoted the development of molecules with antiviral activity. Viral infections are difficult to treat because viruses share many of the host cell metabolic processes and it´s difficult to find drugs with a selective toxicity that only act on the virus. However, there are some enzymes that are specific for certain viruses, allowing the development of antiviral that act by inhibition of those viral enzymes, thus presenting a lower toxicity to the host. Most of the antivirals that are used today are nucleoside analogues, from the earliest, acyclovir, which targets DNA polymerase, to the most recent, sofosbuvir, which targets RNA polymerase. In order to achieve a better oral bioavailability and/or decrease the toxicity to the host, the focus has been placed on the development of classic prodrugs.

Advisors/Committee Members: Catarino, Rita, Pimenta, Adriana.

Subjects/Keywords: Atividade antiviral; Análogos de nucleósidos; Toxicidade; Pró-fármacos; Efeitos secundários; HBV; HCV; HHV; Antiviral activity; Nucleoside analogs; Toxicity; Pro-drugs; Side effects; HBV; HCV; HHV; Domínio/Área Científica::Ciências Médicas::Medicina Básica

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❌

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

APA (6^th Edition):

Ferreira, D. F. S. (2017). Análogos de nucleósidos com atividade antiviral. (Thesis). Universidade Fernando Pessoa. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/6567

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):

Ferreira, Daniela Filipa Santos. “Análogos de nucleósidos com atividade antiviral.” 2017. Thesis, Universidade Fernando Pessoa. Accessed March 05, 2021. https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/6567.

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

MLA Handbook (7^th Edition):

Ferreira, Daniela Filipa Santos. “Análogos de nucleósidos com atividade antiviral.” 2017. Web. 05 Mar 2021.

Vancouver:

Ferreira DFS. Análogos de nucleósidos com atividade antiviral. [Internet] [Thesis]. Universidade Fernando Pessoa; 2017. [cited 2021 Mar 05]. Available from: https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/6567.

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

Council of Science Editors:

Ferreira DFS. Análogos de nucleósidos com atividade antiviral. [Thesis]. Universidade Fernando Pessoa; 2017. Available from: https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/6567

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

Rockefeller University

12. Mohammed, Kevin Dominic. Dissecting the Contribution of the Carboxyl-Terminal Domain and Tail of HIV-1 Integrase to Viral Dynamics and Enzymatic Function.

Degree: 2010, Rockefeller University

URL: https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/71

► The Human Immunodeficiency Virus Type-1 (HIV-1) is the causative agent of the Acquired Immune Deficiency Syndrome (AIDS). Combination antiviral therapy has proven to be particularly… (more)

Subjects/Keywords: HIV-1; HAART; antiviral drug therapy; IN (antiviral drugs); viral integrase; carboxyl-terminal domain (CTD); Life Sciences

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

APA (6^th Edition):

Mohammed, K. D. (2010). Dissecting the Contribution of the Carboxyl-Terminal Domain and Tail of HIV-1 Integrase to Viral Dynamics and Enzymatic Function. (Masters Thesis). Rockefeller University. Retrieved from https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/71

Chicago Manual of Style (16^th Edition):

Mohammed, Kevin Dominic. “Dissecting the Contribution of the Carboxyl-Terminal Domain and Tail of HIV-1 Integrase to Viral Dynamics and Enzymatic Function.” 2010. Masters Thesis, Rockefeller University. Accessed March 05, 2021. https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/71.

MLA Handbook (7^th Edition):

Mohammed, Kevin Dominic. “Dissecting the Contribution of the Carboxyl-Terminal Domain and Tail of HIV-1 Integrase to Viral Dynamics and Enzymatic Function.” 2010. Web. 05 Mar 2021.

Vancouver:

Mohammed KD. Dissecting the Contribution of the Carboxyl-Terminal Domain and Tail of HIV-1 Integrase to Viral Dynamics and Enzymatic Function. [Internet] [Masters thesis]. Rockefeller University; 2010. [cited 2021 Mar 05]. Available from: https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/71.

Council of Science Editors:

Mohammed KD. Dissecting the Contribution of the Carboxyl-Terminal Domain and Tail of HIV-1 Integrase to Viral Dynamics and Enzymatic Function. [Masters Thesis]. Rockefeller University; 2010. Available from: https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/71

University of Gothenburg / Göteborgs Universitet

13. Ekblad, Maria. Anti-herpes simplex virus activities of sulfomannan oligosaccharide PI-88 and disulfated cyclitols.

Degree: 2007, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/4600

► Herpes simplex virus (HSV) initiates invasion of human cells by binding to the cell surface heparan sulfate (HS) glycosaminoglycan chains. This step is mediated by… (more)

▼ Herpes simplex virus (HSV) initiates invasion of human cells by binding to the cell surface heparan sulfate (HS) glycosaminoglycan chains. This step is mediated by the viral envelope glycoproteins gC and/or gB. Sulfated polysaccharides are compounds that mimic the structure of HS chains, and therefore are capable of inhibiting HSV attachment to and subsequent infection of cells. However the high molecular weight and associated with it poor tissue-penetrating activity have limited potential antiviral application of sulfated polysaccharides in humans. Here we found that the HS mimetic PI-88, a sulfomannan oligosaccharide of low molecular weight, efficiently reduced, in contrast to conventional sulfated polysaccharides, the cell-to-cell spread of HSV. Analogues of PI-88 with chemical modifications based on the introduction of specific hydrophobic/aromatic group(s) at the reducing end of PI-88 oligosaccharide chain showed enhanced capability to inhibit infection of cells and the cell-to-cell transmission of HSV and respiratory syncytial virus (RSV). One of these analogues (denoted 536), prepared by modification of PI-88 with cholestanol group, exhibited in contrast to the parental compound an HSV-inactivating activity. Furthermore, several disulfated cyclitols, identified by screening for an anti-HSV activity of a large number of low molecular weight sulfated compounds, efficiently reduced the cell-to-cell spread of HSV and demonstrated the HSV-inactivating activity. The second aim of this thesis was to elucidate the molecular basis for viral resistance to PI-88. Variants of HSV type 1 (HSV-1) and type 2 (HSV-2), selected for by virus propagation in cultured cells in the presence of PI-88 were analysed. Many of these variants had a low infectious titer, indicative of a profound impairment in biological activities of the virus in response to continuous pressure from the drug. These variants were substantially resistant to PI-88 presence during their initial infection of cells and/or their cell-to-cell spread. Nucleotide sequence analysis revealed that PI-88 targeted predominantly the viral envelope glycoproteins that comprise mucin-like region(s), i.e., glycoprotein gC of HSV-1 and glycoprotein gG of HSV-2. The deletion of the mucin-like region of HSV-1 gC (amino acids 33-116) or the deletion of whole HSV-2 gG provided the virus with selective advantage to attach to and to infect cells in the presence of PI-88. In conclusion, we have identified several novel antiviral compounds. One of these compounds, the PI-88 analogue 536, seems to be an attractive candidate for the development of a topical virucide for prevention of genital HSV infections in humans. We have also identified a novel biological function of HSV-2 gG, i.e., its targeting by sulfated oligosaccharides, which suggests involvement of this protein in HSV-2 attachment to cells or in modulation of this step.

Subjects/Keywords: herpes simplex virus; antiviral drugs; viral glycoproteins; heparan sulfate mimetic; PI-88

Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Ekblad, M. (2007). Anti-herpes simplex virus activities of sulfomannan oligosaccharide PI-88 and disulfated cyclitols. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/4600

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):

Ekblad, Maria. “Anti-herpes simplex virus activities of sulfomannan oligosaccharide PI-88 and disulfated cyclitols.” 2007. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed March 05, 2021. http://hdl.handle.net/2077/4600.

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

MLA Handbook (7^th Edition):

Ekblad, Maria. “Anti-herpes simplex virus activities of sulfomannan oligosaccharide PI-88 and disulfated cyclitols.” 2007. Web. 05 Mar 2021.

Vancouver:

Ekblad M. Anti-herpes simplex virus activities of sulfomannan oligosaccharide PI-88 and disulfated cyclitols. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2007. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/2077/4600.

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

Council of Science Editors:

Ekblad M. Anti-herpes simplex virus activities of sulfomannan oligosaccharide PI-88 and disulfated cyclitols. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2007. Available from: http://hdl.handle.net/2077/4600

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

University of Minnesota

14. Seneviratne, Uthpala Indrajith. Exocyclic deoxyadenosine adducts: from environmental carcinogens to antiviral drugs.

Degree: PhD, Chemistry, 2010, University of Minnesota

URL: http://purl.umn.edu/95614

► 1,2,3,4-Diepoxybutane (DEB) is considered the ultimate carcinogenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant present in urban air. Although it preferentially modifies… (more)

▼ 1,2,3,4-Diepoxybutane (DEB) is considered the ultimate carcinogenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant present in urban air. Although it preferentially modifies guanine bases within DNA, DEB induces a large number of A → T transversions, suggesting that it forms strongly mispairing lesions at adenine nucleobases. Three potentially mispairing exocyclic adenine lesions of DEB, N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2'-deoxyadenosine (compound 2), 1,N6-(2-hydroxy- 3-hydroxymethylpropan-1,3-diyl)-2'-deoxyadenosine (compound 3), and 1,N6-(1- hydroxymethyl-2-hydroxypropan-1,3-diyl)-2'-deoxyadenosine (compound 4), have been recently identified in the present work. The structures and stereochemistry of the novel DEB-dA adducts were determined by a combination of UV and NMR spectroscopy, tandem mass spectrometry, and independent synthesis. We found that synthetic N6-(2- hydroxy-3,4-epoxybut-1-yl)-2'-deoxyadenosine (compound 1) representing the product of N6-adenine alkylation by DEB spontaneously cyclizes to form 3 under aqueous conditions or 2 under anhydrous conditions in the presence of organic base. Compound 3 can be interconverted with 4 by a reversible unimolecular pericyclic reaction favoring 4 as a more thermodynamically stable product. Both 3 and 4 are present in double stranded DNA treated with DEB in vitro and in liver DNA of laboratory mice exposed to 1,3- butadiene by inhalation. We propose that in DNA under physiological conditions, DEB alkylates the N-1 position of adenine in DNA to form N1-(2-hydroxy-3,4-epoxybut-1-yl)- adenine adducts, which undergo an SN2-type intramolecular nucleophilic substitution and rearrangement to give 3 (minor) and 4 (major). A post-synthetic methodology for preparing DNA oligomers containing stereo- and site-specific 2 and 3 was developed in v order to investigate their biological properties. DNA oligomers containing site specific 6- chloropurine were coupled with optically pure 1-amino-2-hydroxy-3,4-epoxybutanes to generate oligomers containing compound 1, followed by their spontaneous cyclization to 1,N6-γ-HMHP-dA lesions. N6,N6-DHB-dA containing strands were prepared analogously by coupling 6-chloropurine containing DNA with 3S,4S or 3R,4R pyrrolidine-3,4-diols. Oligodeoxynucleotide structures were confirmed by ESI- MS, exonuclease ladder sequencing, and HPLC-MS/MS of enzymatic digests. UV melting and CD spectroscopy studies of DNA duplexes containing N6,N6-DHB-dA and 1,N6-γ-HMHP-dA revealed that both lesions lower the thermodynamic stability of DNA when paired with dT. However, the stability of 1,N6-γ-HMHP-dA containing DNA duplexes was greater when adenine residue was placed opposite the lesion, suggesting that DEB-dA adducts preferentially pair with A, potentially leading to A → T transversions during DNA replication. Solution state NMR and site specific mutagenesis were conducted to further test the role of exocyclic DEB-dA adducts in mutagenesis. In the second part of this work, a series…

Subjects/Keywords: Antiviral drugs; Carcinogens; Deoxyadenosine adducts; DNA oligomers; Exocyclic adducts; Polymerase bypass; Chemistry

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❌

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

APA (6^th Edition):

Seneviratne, U. I. (2010). Exocyclic deoxyadenosine adducts: from environmental carcinogens to antiviral drugs. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/95614

Chicago Manual of Style (16^th Edition):

Seneviratne, Uthpala Indrajith. “Exocyclic deoxyadenosine adducts: from environmental carcinogens to antiviral drugs.” 2010. Doctoral Dissertation, University of Minnesota. Accessed March 05, 2021. http://purl.umn.edu/95614.

MLA Handbook (7^th Edition):

Seneviratne, Uthpala Indrajith. “Exocyclic deoxyadenosine adducts: from environmental carcinogens to antiviral drugs.” 2010. Web. 05 Mar 2021.

Vancouver:

Seneviratne UI. Exocyclic deoxyadenosine adducts: from environmental carcinogens to antiviral drugs. [Internet] [Doctoral dissertation]. University of Minnesota; 2010. [cited 2021 Mar 05]. Available from: http://purl.umn.edu/95614.

Council of Science Editors:

Seneviratne UI. Exocyclic deoxyadenosine adducts: from environmental carcinogens to antiviral drugs. [Doctoral Dissertation]. University of Minnesota; 2010. Available from: http://purl.umn.edu/95614

Kyoto University

15. GHOSH, Gopal Chandra. Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition .

Degree: 2009, Kyoto University

URL: http://hdl.handle.net/2433/85391

► The concern for pharmaceutically active compounds (PhACs) as contaminants in the environment and the need to assess their environmental risk have greatly increased since the… (more)

▼ The concern for pharmaceutically active compounds (PhACs) as contaminants in the environment and the need to assess their environmental risk have greatly increased since the early nineties. Among PhACs, antibiotics and antiviral drugs are of important concern due to their role in growing antibiotic and antiviral drugs resistance among pathogenic bacteria and influenza viruses, respectively. Besides resistance issue, the compounds may upset sensitive ecosystems as they are designed to be highly bioactive. Clinically-important antibiotics are virtually ubiquitous contaminants in sewage water and surface water. Notably, recent emergence of novel influenza and use of anti-influenza drugs (specially Tamiflu®) during seasonal influenza、 influenza epidemics and for future pandemic are of emerging concern. Every year seasonal influenza epidemic causes tens of millions of respiratory illnesses and 250, 000 to 500, 000 deaths worldwide. WHO (World Health Organization) recommend the use of antiviral drug Tamiflu® during pandemic, as they are easy to use. Currently only Japan uses over eighty percent of Tamiflu® prescribed globally during common seasonal influenza. It is a fact that a huge amount of antiviral drugs and antibiotics ( for post infection cure of respiratory illness) will be used during an influenza pandemic and will arrive to sewage treatment plants (STPs).Unfortunately, these compounds behaviors are mostly unknown in both conventional and advanced STPs. The exposure of antiviral drug in the wild fowl gut and its implications for hastening the generation of antiviral-resistance in avian influenza viruses are also an emerging issue. The major objective of this thesis work was to investigate the occurrence of antibiotics and antiviral drugs in sewage treatment plants and their fate in different sewage treatment plants. The specific objectives were as follows: (a) to established appropriate analytical method for the selected antibiotics and antiviral drugs in sewage treatment plants, (b) to investigate the occurrence and removal of antibiotics and antiviral drugs in sewage treatment plants differ in technology and operation conditions; and (c) to predicts environmental concentration of the target compounds during a pandemics and appraisal of appropriate technology to reduce the risk associated with widespread use under pandemic conditions. In this study we selected twenty antibiotics: one beta-lactam: ampicillin; four macrolides: azithromycin, clarithromycin and roxithromycin; five quinolones: ciprofloxacin, enrofloxacin, levofloxacin, nalidixic acid and norfloxacin; two tetracycline: tetracycline and oxytetracycline; five sulfonamides: sulfadimethoxine, sulfadimizine, sulfamerazine, sulfam- ethoxazole and sulfamonomethoxine; and four others: lincomycin, novobiocin, salinomycin and trimethoprim. Oseltamivir Carboxylate (OC), the active metabolite of oseltamivir phosphate (Tamiflu®) and amantadine (AMN) were selected as antiviral drugs. This dissertation consists of nine chapters: Chapter I describe the background and… Advisors/Committee Members: 田中, 宏明 (advisor), 伊藤, 禎彦 (advisor), 藤井, 滋穂 (advisor).

Subjects/Keywords: LC/MS/MS; Antibiotics; Antiviral Drugs; Sewage Treatment Plants; Pandemic Influenza

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APA (6^th Edition):

GHOSH, G. C. (2009). Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/85391

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):

GHOSH, Gopal Chandra. “Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition .” 2009. Thesis, Kyoto University. Accessed March 05, 2021. http://hdl.handle.net/2433/85391.

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

MLA Handbook (7^th Edition):

GHOSH, Gopal Chandra. “Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition .” 2009. Web. 05 Mar 2021.

Vancouver:

GHOSH GC. Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition . [Internet] [Thesis]. Kyoto University; 2009. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/2433/85391.

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

Council of Science Editors:

GHOSH GC. Behavior of antibiotics and antiviral drugs in sewage treatment plants and risk associated with their widespread use under pandemic condition . [Thesis]. Kyoto University; 2009. Available from: http://hdl.handle.net/2433/85391

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

Texas Christian University

16. Lei, Xiangyang. Design, syntheses and biological activities of L-chicoric acid analogues as HIV-1 integrase inhibitors.

Degree: PhD, 2006, Texas Christian University

URL: https://repository.tcu.edu:443/handle/116099117/3932

Subjects/Keywords: HIV (Viruses); AIDS (Disease); Virus inhibitors.; Antiviral agents.; Drugs Design.

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

APA (6^th Edition):

Lei, X. (2006). Design, syntheses and biological activities of L-chicoric acid analogues as HIV-1 integrase inhibitors. (Doctoral Dissertation). Texas Christian University. Retrieved from https://repository.tcu.edu:443/handle/116099117/3932

Chicago Manual of Style (16^th Edition):

Lei, Xiangyang. “Design, syntheses and biological activities of L-chicoric acid analogues as HIV-1 integrase inhibitors.” 2006. Doctoral Dissertation, Texas Christian University. Accessed March 05, 2021. https://repository.tcu.edu:443/handle/116099117/3932.

MLA Handbook (7^th Edition):

Lei, Xiangyang. “Design, syntheses and biological activities of L-chicoric acid analogues as HIV-1 integrase inhibitors.” 2006. Web. 05 Mar 2021.

Vancouver:

Lei X. Design, syntheses and biological activities of L-chicoric acid analogues as HIV-1 integrase inhibitors. [Internet] [Doctoral dissertation]. Texas Christian University; 2006. [cited 2021 Mar 05]. Available from: https://repository.tcu.edu:443/handle/116099117/3932.

Council of Science Editors:

Lei X. Design, syntheses and biological activities of L-chicoric acid analogues as HIV-1 integrase inhibitors. [Doctoral Dissertation]. Texas Christian University; 2006. Available from: https://repository.tcu.edu:443/handle/116099117/3932

Utah State University

17. Burns, Noah Jefferson, III. Characterization of Anti-Pichinde Virus Monoclonal Antibodies for the Directed Delivery of Antiviral Drugs and Toxins.

Degree: PhD, Biology, 1989, Utah State University

URL: https://digitalcommons.usu.edu/etd/4360

► Mouse monoclonal antibodies directed against Pichinde virus (PCV) were produced to evaluate their application as vehicles for the delivery of antiviral drugs or toxins… (more)

▼ Mouse monoclonal antibodies directed against Pichinde virus (PCV) were produced to evaluate their application as vehicles for the delivery of antiviral drugs or toxins to virus-infected cells. Four monoclonal antibodies, PC4.9A6, PC4.9D3, PC4.7C2, and PC4.8D3, were of the IgG2a subisotype and reacted with acetone-fixed and live PCV-infected Vero-76 cells. In vivo stained splenic macrophages derived from PCV-infected hamsters that had been injected with fluorescein-labeled PC4.9A6 (FITC9A6) demonstrated a 400% increase in total fluorescence over similarly treated, non-infected cells when analyzed by flow cytometry. This is an indication that FITC-9A6 does have some ability to specifically target PCV infected cells in vivo. Radioimmunoprecipitation of viral proteins showed that all the antibodies precipitated two different PCV proteins, one of 64,000 daltons and another of 38,000 daltons. These proteins are, respectively, PCV ix nucleoprotein (NP) and a breakdown product of NP that is present in PCV infected cells. An immunofluorescent assay (IFA) for PCV was developed. This IFA was used for antiviral drug assays against PCV. The assay was performed by adding fluorescein-labeled anti-PCV monoclonal antibody to fixed, virus infected cells at 24 h after infection and counting the fluorescent cells. The 50% effective dose (EDso) for ribavirin against PCV using this IFA was 6.0 IJ. g/ml. The EDso of ribavirin using inhibition of marginal PCV cytopathogenic effect after 12 days was 6.0 IJ. g/ml and using plaque reduction after 5 days is 2.5 IJ. g/ml, indicating that this IFA was of comparable sensitivity. An immunotoxin (IT) was produced by the conjugation of gelonin to PC4.9A6. This IT was tested in vivo in PCV-infected MHA hamsters. It was not active against the disease at the dosage tested and by the intraperitoneal (i.p.) treatment route employed in this study. The positive control, ribavirin, administered i.p. for 14 days at a dosage of 40 mg/ ml significantly increased the number of survivors. Three of 5 IT toxicity control animals developed some humoral response that inhibited PC4.9A6 binding to infected cells. They did not show any humoral response to the gelonin moiety of the IT. Advisors/Committee Members: Robert W. Sidwell, ;.

Subjects/Keywords: Characterization; Anti-Pichinde Virus; Monoclonal Antibodies; Directed Delivery; Antiviral Drugs; Toxins; Biology

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APA (6^th Edition):

Burns, Noah Jefferson, I. (1989). Characterization of Anti-Pichinde Virus Monoclonal Antibodies for the Directed Delivery of Antiviral Drugs and Toxins. (Doctoral Dissertation). Utah State University. Retrieved from https://digitalcommons.usu.edu/etd/4360

Chicago Manual of Style (16^th Edition):

Burns, Noah Jefferson, III. “Characterization of Anti-Pichinde Virus Monoclonal Antibodies for the Directed Delivery of Antiviral Drugs and Toxins.” 1989. Doctoral Dissertation, Utah State University. Accessed March 05, 2021. https://digitalcommons.usu.edu/etd/4360.

MLA Handbook (7^th Edition):

Burns, Noah Jefferson, III. “Characterization of Anti-Pichinde Virus Monoclonal Antibodies for the Directed Delivery of Antiviral Drugs and Toxins.” 1989. Web. 05 Mar 2021.

Vancouver:

Burns, Noah Jefferson I. Characterization of Anti-Pichinde Virus Monoclonal Antibodies for the Directed Delivery of Antiviral Drugs and Toxins. [Internet] [Doctoral dissertation]. Utah State University; 1989. [cited 2021 Mar 05]. Available from: https://digitalcommons.usu.edu/etd/4360.

Council of Science Editors:

Burns, Noah Jefferson I. Characterization of Anti-Pichinde Virus Monoclonal Antibodies for the Directed Delivery of Antiviral Drugs and Toxins. [Doctoral Dissertation]. Utah State University; 1989. Available from: https://digitalcommons.usu.edu/etd/4360

North-West University

18. Scholtz, Daniël Jacobus. Prescribing patterns of antiretroviral drugs in the private health care sector in South Africa : a drug utilisation review / Daniël Jacobus Scholtz .

Degree: 2005, North-West University

URL: http://hdl.handle.net/10394/1723

► HIV/AIDS is already the leading cause of death worldwide (Unicef et al., 2004:10) with more than 5 million people out of a total of 46… (more)

▼ HIV/AIDS is already the leading cause of death worldwide (Unicef et al., 2004:10) with more than 5 million people out of a total of 46 million South Africans that were HIV positive in 2004, giving a total population prevalence rate of 11 per cent (Dorrington et al., 2004:1). Many people infected do not have access to even the basic drugs needed to treat HIV-related infections and other conditions (Wikipedia, 2004:3). The relative high price of many of the antiretroviral (ARV) drugs and diagnostics on the other hand are one of the main barriers to their availability in developing countries (Unicef et al., 2004:77). ARV drugs registered in South Africa include the Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and Protease Inhibitors (PIs) (MCC, 2004:1). The objective of this study was to review, analyse and interpret the prescribing patterns of antiviral drugs, with special reference to antiretroviral drugs, in the private health care sector in South Africa by using a medicine claims database. A quantitative, retrospective drug utilisation review was performed. The data ranging from 1 January 2001 to 31 December 2001, 1 January 2002 to 31 December 2002, and 1 January 2004 to 31 December 2004 were used, dividing each year into three four-month periods, namely January to April, May to August, and September to December. It was found that 0.38 per cent (n=1 475 380) for 2001, 0.72 per cent (n=2 076 236) for 2002, and 1.68 per cent (n=2 595 254) for 2004 of all studied prescriptions for the research periods 2001, 2002, and 2004 respectively, contained ARV drugs. ARV drugs constituted 0.33 per cent (n=2 951 326) for 2001, 0.87 per cent (n=4 042 145) for 2002, and 1.92 per cent (n=5 305 882) for 2004 of the total number of medicine items prescribed for the study years 2001, 2002 and 2004 respectively. The total cost of ARV drugs amounted to R4 990 784.29, thus constituting 1.31 per cent of the total cost (R379 708 489) of all medicine items on the database for 2001, increased to R18 235 075.75, thus constituting 3.03 per cent of the total cost (R601 350 325) of all medicine items on the database for 2002, and increased to R34 714 483.64, thus constituting 5.25 per cent of the total cost (R661 223 146) of all medicine items on the database for 2004. It was found that 35.31 per cent (n=5 599) for 2001, 52.68 per cent (n=15 004) for 2002, and 74.27 per cent (n=43 482) for 2004 of all studied antiviral prescriptions for the research periods 2001, 2002, and 2004 respectively, contained ARV drugs. ARV drugs constituted 46.25 per cent (n=21 183) for 2001, 70.20 per cent (n=50 246) for 2002, and 85.87 per cent (n=118 718) for 2004 of the total number of antiviral medicine items prescribed for the study years 2001, 2002 and 2004 respectively. The total cost of ARV medicine items, represented 67.33 per cent (n=R4 990 784.29) during 2001, 84.72 per cent (n=R18 235 075.75) during 2002, and 91.20 per cent (n=R34 714 483.64) during 2004 of the total cost of all…

Subjects/Keywords: HIV/AIDS; Antiviral drugs; Antiretroviral (ARV) drugs; Managed care; Pharmacoeconomics; Drug utilisation review; Disease management; Prevalence and medicine treatment cost; Average cost; Single exit price; Cost savings

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APA (6^th Edition):

Scholtz, D. J. (2005). Prescribing patterns of antiretroviral drugs in the private health care sector in South Africa : a drug utilisation review / Daniël Jacobus Scholtz . (Thesis). North-West University. Retrieved from http://hdl.handle.net/10394/1723

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):

Scholtz, Daniël Jacobus. “Prescribing patterns of antiretroviral drugs in the private health care sector in South Africa : a drug utilisation review / Daniël Jacobus Scholtz .” 2005. Thesis, North-West University. Accessed March 05, 2021. http://hdl.handle.net/10394/1723.

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

MLA Handbook (7^th Edition):

Scholtz, Daniël Jacobus. “Prescribing patterns of antiretroviral drugs in the private health care sector in South Africa : a drug utilisation review / Daniël Jacobus Scholtz .” 2005. Web. 05 Mar 2021.

Vancouver:

Scholtz DJ. Prescribing patterns of antiretroviral drugs in the private health care sector in South Africa : a drug utilisation review / Daniël Jacobus Scholtz . [Internet] [Thesis]. North-West University; 2005. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10394/1723.

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

Council of Science Editors:

Scholtz DJ. Prescribing patterns of antiretroviral drugs in the private health care sector in South Africa : a drug utilisation review / Daniël Jacobus Scholtz . [Thesis]. North-West University; 2005. Available from: http://hdl.handle.net/10394/1723

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

19. Le, Ly. Incorporating molecular dynamics simulations into drug design targeting Influenza N1 Neuraminidases.

Degree: PhD, Chemistry, 2011, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/13/rec/1341

► The FDA antiviral drug, Tamiflu (oseltamivir) is the front-line antiviral drug for the fight against 2003 avian flu (H5N1) as well as, more recently, for… (more)

▼ The FDA antiviral drug, Tamiflu (oseltamivir) is the front-line antiviral drug for the fight against 2003 avian flu (H5N1) as well as, more recently, for the 2009 swine flu (H1N1pdm). The drug functions as a neuraminidase inhibitor that prevents the release of new virions. Unfortunately, there is emerging evidence that the neuraminidase mutations H274Y and N294S render oseltamivir ineffective against the H5N1 virus. Of greater concern is the growing likelihood of the emergence of similar oseltamivir-resistant strains of H1N1pdm. It is therefore critical to understand the mechanisms for mutation-induced drug resistance in the H5N1 and H1N1pdm flu viruses in order to develop new and effective therapies. As molecular dynamics (MD) simulations have become an important tool for the study of biological systems, this dissertation aims to employ MD simulations for computer-aided rational drug design. Specifically, different MD simulation techniques were utilized in the investigation of oseltamivir-resistant mechanisms of H5N1/H1N1pdm and for the development of new antiviral drugs. Chapter 1 is simply a general introduction to the whole thesis. Chapter 2 presents top-hits for H1N1pdm neuraminidase identified by virtual screening using ensemblebased docking technique, which incorporates protein flexibility into molecular docking. Next in Chapter 3, progress in the development of two related methodologies for calculation of solvation free energy, one called the Coupled Reference Interaction Site model-hyper-netted chain/molecular dynamics (RISM/MD) approach, and another called Molecular Mechanics Poisson?Boltzmann linear response approximation and surface area contributions (MMPB-LRA-SA), are presented. The methods are expected to be applicable to the lead refinement process since they provide more reliable results than the continuum model but are less computationally expensive than conventional MD methods. In Chapter 4, we discuss our observations based on drug-protein endpoint interactions on how the mutations H274Y and N294S induce oseltamivir resistance in neuraminidase N1 subtypes. However, since the two mutations are non-active-site, endpoint interactions alone cannot fully account for the drug resistance. In Chapter 5, we present our finding of the drug binding pathway through electrostatic surface potential and steered MD simulation. The results reveal a novel oseltamivir-resistant mechanism in which the mutations rupture the drug binding funnel, in conjuction with the findings reported in Chapter 4. Our study not only assists understanding of oseltamivir-resistance in neuraminidase N1 subtypes, but also bears several important consequences for the intelligent design of new inhibitors that can overcome the established resistance strain.

Subjects/Keywords: Drug design; Drug resistant; Influenza; MD simulation; Neuraminidase inhibitors; Influenza neuraminidases; Antiviral drugs

…antiviral drugs. Due to their ability to mutate quickly, the viruses can easily survive people’s… …neuraminidase as well as intelligent design of new antiviral drugs that work for established drug… …against influenza A virus. CHAPTER 2 PROMISING ANTIVIRAL DRUGS FOR SWINE FLU H1N1PDM REVEALED… …promising antiviral drugs against the H1N1pdm neuraminidase, using the ensemble-based docking… …of hydrogen bond (in percent) for binding site residues with known drugs and top…

10 more images…

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APA (6^th Edition):

Le, L. (2011). Incorporating molecular dynamics simulations into drug design targeting Influenza N1 Neuraminidases. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/13/rec/1341

Chicago Manual of Style (16^th Edition):

Le, Ly. “Incorporating molecular dynamics simulations into drug design targeting Influenza N1 Neuraminidases.” 2011. Doctoral Dissertation, University of Utah. Accessed March 05, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/13/rec/1341.

MLA Handbook (7^th Edition):

Le, Ly. “Incorporating molecular dynamics simulations into drug design targeting Influenza N1 Neuraminidases.” 2011. Web. 05 Mar 2021.

Vancouver:

Le L. Incorporating molecular dynamics simulations into drug design targeting Influenza N1 Neuraminidases. [Internet] [Doctoral dissertation]. University of Utah; 2011. [cited 2021 Mar 05]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/13/rec/1341.

Council of Science Editors:

Le L. Incorporating molecular dynamics simulations into drug design targeting Influenza N1 Neuraminidases. [Doctoral Dissertation]. University of Utah; 2011. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd3/id/13/rec/1341

20. Shen, Hong. Hepatitis C infection models : Modèles d'infection de l'hépatite C.

Degree: Docteur es, Virologie, 2012, Université Paris Descartes – Paris V

URL: http://www.theses.fr/2012PA05T016

► L'hépatite C (VHC) est l'une des causes principales de maladies du foie dans le monde, qui représentent un risque élevé d'évoluer vers la cirrhose et… (more)

▼ L'hépatite C (VHC) est l'une des causes principales de maladies du foie dans le monde, qui représentent un risque élevé d'évoluer vers la cirrhose et le carcinome hépatocellulaire. Actuellement, le traitement standard de l’infection par le VHC est l'interféron pégylé-(peg-IFN) et la ribavirine. Bien que le taux de la réponse virale soutenue (RVS) au traitement se soit améliorée au cours de ces années, cette thérapie n'est pas efficace chez tous les patients. En outre, plusieurs effets secondaires toxiques, de complications et le coût élevé limitent la compliance du patient et l'efficacité du traitement. Il n'existe pas de modèle simple d'infection par le VHC et il est nécessaire de développer des modèles in vitro et in vivo utiles pour étudier la physiopathologie de l'infection par le VHC, y compris les événements précoces de l'infection aiguë (l'entrée du virus, des mécanismes immunologiques et génétiques prédictifs) ainsi que l'évaluation de la puissance des médicaments antiviraux contre le VHC. Nous rapportons ici, nos efforts visant à développer des modèles appropriés de l'infection par le VHC. Dans un premier temps, nous avons établi un modèle de petit animal pour étudier l'infection par le VHC. Tupaia est un petit animal, apparenté aux primates et peu couteux. Dans notre travail, nous avons étudié la susceptibilité du tupaia à l'infection par VHC. Douze tupaias adultes ont été inoculés avec le VHC provenant de sérum de patient et d'ARN du VHC (génotype 1a). Trois jeunes tupaias ont été artificiellement nourris pendant un mois et ensuite inoculés par le VHC provenant de sérum du patient. L'ARN du VHC, les anticorps anti-VHC et l’évolution des quasi-espèces du VHC ont été déterminées chez l'animal avant et après l'inoculation. L'infection transitoire et intermittente s'est produite chez deux des 3 jeunes tupaias et l’infection chronique par le VHC s’est produite chez quatre tupaias sur 12 tupaias adultes. Le tupaia devrait représenter un modèle utile pour l'étude de l’infection chronique par le VHC. Dans une deuxième étape, un système de culture in vitro d'hépatocytes primaires de Tupaia a été établi, dans lequel l'infection par le VHC ne pouvait être bloquée ni par le CD81 soluble ni par des anticorps dirigés contre le CD81. Pour comprendre ces résultats, nous avons cloné, séquencé la grande boucle extracellulaire (LEL) du CD81 chez le Tupaia et analysé l'interaction de la protéine d’enveloppe E2 du VHC avec la LEL du CD81 chez le Tupaia par un test « enzyme-linked immunosorbent assay » (EIA). Nous avons constaté que chez le Tupaia, la séquence d'acides aminés du LEL de CD81 qui se lie au VHC présentait en 6 résidus d'acides aminés différents par rapport à la séquence humaine et la capacité de LEL de CD81 à se lier à la proteine d’enveloppe E2 du VHC a également diminuée. La structure différente de CD81 chez l’homme et chez le tupaia pourrait expliquer l'altération de l'interaction entre CD81 et la proteine E2 du VHC. Ce résultat démontre un rôle important de LEL du CD81 pour l'entrée du VHC. Dans une troisième… Advisors/Committee Members: Pol, Stanislas (thesis director), Lagaye, Sylvie (thesis director).

Subjects/Keywords: Virus de l’Hépatite C (VHC); Modèle animal; Tupaia; CD81; Culture de tissus; Propagation du virus; Physiologie hépatocellulaire; Essai des drogues antivirales; Hepatitis C virus (HCV); Animal model; Tupaia; CD81; Tissue culture; Virus spreading; Hepatocellular physiology; Antiviral drugs assay

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

APA (6^th Edition):

Shen, H. (2012). Hepatitis C infection models : Modèles d'infection de l'hépatite C. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2012PA05T016

Chicago Manual of Style (16^th Edition):

Shen, Hong. “Hepatitis C infection models : Modèles d'infection de l'hépatite C.” 2012. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed March 05, 2021. http://www.theses.fr/2012PA05T016.

MLA Handbook (7^th Edition):

Shen, Hong. “Hepatitis C infection models : Modèles d'infection de l'hépatite C.” 2012. Web. 05 Mar 2021.

Vancouver:

Shen H. Hepatitis C infection models : Modèles d'infection de l'hépatite C. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2012. [cited 2021 Mar 05]. Available from: http://www.theses.fr/2012PA05T016.

Council of Science Editors:

Shen H. Hepatitis C infection models : Modèles d'infection de l'hépatite C. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2012. Available from: http://www.theses.fr/2012PA05T016

University of Texas – Austin

21. Xia, Shuangluo. High throughput screening of inhibitors for influenza protein NS1.

Degree: PhD, Biochemistry, 2009, University of Texas – Austin

URL: http://hdl.handle.net/2152/14126

► Influenza virus A and B are common pathogens that cause respiratory disease in humans. Recently, a highly virulent H5N1 subtype avian influenza virus caused disease… (more)

▼ Influenza virus A and B are common pathogens that cause respiratory disease in humans. Recently, a highly virulent H5N1 subtype avian influenza virus caused disease outbreaks in poultry around the world. Drug resistant type A viruses rapidly emerged, and the recent H5N1 viruses were reported to be resistant to all current antiviral drugs. There is an urgent need for the development of new antiviral drugs target against both influenza A and B viruses. This dissertation describes work to identify small molecule inhibitors of influenza protein NS1 by a high throughput fluorescence polarization assay. The N-terminal GST fusion of NS1A (residue 1-215) and NS1B (residue 1-145) were chosen to be the NS1A and NS1B targets respectively for HT screening. In developing the assay, the concentrations of fluorophore and protein, and chemical additives were optimized. A total of 17,969 single chemicals from four compound libraries were screened using the optimized assay. Six true hits with dose-response activity were identified. Four of them show an IC₅₀ less than 1 [micromolar]. In addition, one compound, EGCG, has proven to reduce influenza virus replication in a cell based assay, presumably by interacting with the RNA binding domain of NS1. High throughput, computer based, virtual screenings were also performed using four docking programs. In terms of enrichment rate, ICM was the best program for virtual screening inhibitors against NS1-RBD. The compound ZINC0096886 was identified as an inhibitor showing an IC₅₀ around 19 [micromolars] against NS1A, and 13.8 [micromolars] against NS1B. In addition, the crystallographic structures of the NS1A effector domain (wild type, W187A, and W187Y mutants) of influenza A/Udorn/72 virus are presented. A hypothetical model of the intact NS1 dimer is also presented. Unlike the wild type dimer, the W187Y mutant behaved as a monomer in solution, but still was able to binding its target protein, CPSF30, with wild type binding affinity. This mutant may be a better target for the development of new antiviral drugs, as the CPSF30 binding pocket is more accessible to potential inhibitors. The structural information of those proteins would be very helpful for virtual screening and rational lead optimization. Advisors/Committee Members: Robertus, Jon D. (advisor).

Subjects/Keywords: Influenza protein inhibitors; Influenza protein NS1; Antiviral drugs; Fluorescence polarization assay; Binding affinity; NS1A; NS1B; Virtual screening; NS1

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APA (6^th Edition):

Xia, S. (2009). High throughput screening of inhibitors for influenza protein NS1. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/14126

Chicago Manual of Style (16^th Edition):

Xia, Shuangluo. “High throughput screening of inhibitors for influenza protein NS1.” 2009. Doctoral Dissertation, University of Texas – Austin. Accessed March 05, 2021. http://hdl.handle.net/2152/14126.

MLA Handbook (7^th Edition):

Xia, Shuangluo. “High throughput screening of inhibitors for influenza protein NS1.” 2009. Web. 05 Mar 2021.

Vancouver:

Xia S. High throughput screening of inhibitors for influenza protein NS1. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2009. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/2152/14126.

Council of Science Editors:

Xia S. High throughput screening of inhibitors for influenza protein NS1. [Doctoral Dissertation]. University of Texas – Austin; 2009. Available from: http://hdl.handle.net/2152/14126

22. Badillo, Aurélie. Analyses structurales et fonctionnelles de la protéine non-structurale 5A (NS5A) du virus de l’hépatite C : Structural and functional analysis of the non structural protein 5A (NS5A) from hepatitis C virus.

Degree: Docteur es, Biochimie, 2012, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2012LYO10239

►

La protéine NS5A est essentielle pour la réplication et l'assemblage du virus de l'hépatite C (VHC), et elle constitue une cible thérapeutique prometteuse pour le… (more)

▼

La protéine NS5A est essentielle pour la réplication et l'assemblage du virus de l'hépatite C (VHC), et elle constitue une cible thérapeutique prometteuse pour le développement d'antiviraux. Cependant, aucune fonction claire n'a encore été décrite pour NS5A, et les connaissances structurales restent limitées. Ainsi, nous avons caractérisé l'état intrinsèquement désordonné des domaines D2 et D3 de NS5A en décrivant leurs espaces conformationnels et leurs potentialités de repliement en combinant différentes méthodes biophysiques. Nous avons aussi mis en évidence la variabilité structurale du domaine D2 au sein des génotypes du VHC, ce qui pourrait être en rapport avec les différences de pathogénie et d'efficacité des thérapies observées selon les génotypes. L'interaction de D2 et D3 avec la cyclophiline humaine A (CypA) a été étudiée par résonance plasmonique de surface (SPR). Bien que des mutations au sein du domaine D2 rendent la réplication du VHC moins dépendante de la présence de CypA, ces mutations n'empêchent pas la liaison entre D2 et CypA. En revanche, elles induisent des perturbations structurales qui pourraient affecter la cinétique d'interconversion des conformères de D2. Nous avons montré par SPR que D2 et D3 interagissent avec le domaine de fixation à l'ADN du récepteur nucléaire FXR. Cette interaction pourrait inhiber la fixation de FXR sur sa cible ADN, suggérant une implication de NS5A dans la modulation de l'activité transcriptionnelle de ce récepteur nucléaire. L'ensemble de ces informations, nous a permis de proposer un modèle de la structure globale de NS5A permettant une meilleure compréhension des propriétés structurales et fonctionnelles de cette protéine énigmatique

NS5A is essential for HCV replication and particle assembly, and constitutes a very promising drug target. However, no clear function has yet been described for NS5A, and structural knowledge remains limited. We characterized the intrinsically disordered nature of NS5A domains D2 and D3, and describe their folding propensity and their overall conformational behaviour by combining different biophysical methods. We also highlighted the structural variability of D2 domain in HCV genotypes, which might be correlated with the disparities observed between genotypes in terms of pathogenesis and efficiency of therapies. The interactions between D2 and D3 with human cyclophilin A (CypA) was analysed by surface plasmon resonance (SPR). We showed that mutations in the D2 domain conferring resistance of HCV replication to CypA inhibitors did not prevent the interaction between D2 and CypA. However, they induce structural perturbations that may affect the kinetics of conformers interconversion of D2. We also showed by SPR that D2 and D3 interact with the of DNA-binding domain of the nuclear receptor FXR (farnesoid X receptor alpha). This interaction reduce the binding of FXR to its DNA target, suggesting an involvement of NS5A in the modulation of the transcriptional activity of FXR. All this data led us to propose a model of the overall…

Advisors/Committee Members: Penin, François (thesis director).

Subjects/Keywords: Virus de l’hépatite C; NS5A; Protéine intrinsèquement désordonnée (IDP); Antiviraux; Diffusion des rayons X aux petits angles (SAXS); Dichroïsme circulaire; Résonance plasmonique de surface (SPR); Titration calorimétrie isotherme (ITC); Hepatitis C virus (HCV); Non structural protein 5A (NS5A); Intrinsically disordered protein (IDP); Antiviral drugs; Small angle X-ray scattering (SAXS); Circular dichroism; Surface plasmon resonance (SPR); Isothermal titration calorimetry (ITC); 572

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

APA (6^th Edition):

Badillo, A. (2012). Analyses structurales et fonctionnelles de la protéine non-structurale 5A (NS5A) du virus de l’hépatite C : Structural and functional analysis of the non structural protein 5A (NS5A) from hepatitis C virus. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2012LYO10239

Chicago Manual of Style (16^th Edition):

Badillo, Aurélie. “Analyses structurales et fonctionnelles de la protéine non-structurale 5A (NS5A) du virus de l’hépatite C : Structural and functional analysis of the non structural protein 5A (NS5A) from hepatitis C virus.” 2012. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed March 05, 2021. http://www.theses.fr/2012LYO10239.

MLA Handbook (7^th Edition):

Badillo, Aurélie. “Analyses structurales et fonctionnelles de la protéine non-structurale 5A (NS5A) du virus de l’hépatite C : Structural and functional analysis of the non structural protein 5A (NS5A) from hepatitis C virus.” 2012. Web. 05 Mar 2021.

Vancouver:

Badillo A. Analyses structurales et fonctionnelles de la protéine non-structurale 5A (NS5A) du virus de l’hépatite C : Structural and functional analysis of the non structural protein 5A (NS5A) from hepatitis C virus. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2012. [cited 2021 Mar 05]. Available from: http://www.theses.fr/2012LYO10239.

Council of Science Editors:

Badillo A. Analyses structurales et fonctionnelles de la protéine non-structurale 5A (NS5A) du virus de l’hépatite C : Structural and functional analysis of the non structural protein 5A (NS5A) from hepatitis C virus. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2012. Available from: http://www.theses.fr/2012LYO10239

University of St. Andrews

23. Nobre, Rita. Viral interferon antagonists and antiviral drugs .

Degree: 2009, University of St. Andrews

URL: http://hdl.handle.net/10023/818

► For this project, we developed reporter cell lines that express viral proteins with the potential to be used in cell-based screening assays to select chemical… (more)

▼ For this project, we developed reporter cell lines that express viral proteins with the potential to be used in cell-based screening assays to select chemical candidates for antiviral drugs. The viral proteins expressed in these reporter cell lines (Hepatitis B core and precore, Hepatitis C core (1a and 4a), and Rabies P (BH and SADL16)) were presented in the literature as responsible for interfering with the IFN signaling pathway, specifically for blocking the expression of its key protein STAT1. We cloned the viral genes into the pdl’SurvpkIB reporter plasmid and, through a lentiviral delivery system, infected the Hep2Mx1TIPSE cells and the A549Luc cells resulting in the Hep2Mx1TIPSEHBVprecore, Hep2Mx1TIPSEHBVcore, Hep2Mx1TIPSEHCVcore (1a and 4a), and A549lucRabiesP (SADL16 and BH) reporter cell lines. We assessed the obtained viral cell lines according to their ability to block the IFN signaling pathway by using three different assays: an immunoblot targeting the protein STAT1, a phenotypic assay for survival in the presence of puromycin (in viral Hep2Mx1TIPSE cells), and a quantitative measure of luciferase expression (in viral A549Luc cells). Concerning the immunoblot targeting STAT1, the results showed that only cell lines expressing the Rabies P protein (namely the A549lucRabiesPSADL16 cell line) were able to decrease the level of expression of STAT1. The phenotypic assay conducted on the Hep2Mx1TIPSE viral cell lines were intended to show impairment of the IFN signaling pathway through the down-regulation of the IFN stimulated gene Mx1. Normal Hep2Mx1TIPSE cells contain a puromycin resistance gene controlled by the Mx1 promoter. Therefore, when puromycin is added to these cells in the presence of IFN, the signaling pathway is activated and Mx1 as well as the puromycin resistance gene are expressed resulting in cell survival. Results showed that the cell lines expressing the HCV core and HBV precore proteins also survived puromycin addition. However, the Hep2Mx1TIPSEHBVcore cells died in the presence of puromycin suggesting that in these cells the HBVcore protein affects Mx1 protein expression. Since it was expected that all viral cell lines would be able to down- regulate Mx1 by impairing the IFN signaling pathway, it was assumed that the level of viral expression may not have been enough to be detected by this kind of assay and therefore a quantitative study would be crucial for the continuation of this project. The cell lines expressing the Rabies P protein demonstrated their ability to block STAT1 and contained a luciferase gene under the control of an IFN regulated promoter. These cells were therefore considered the best candidates for the quantitative assay. We compared the difference between luciferase expression in the viral cells in the presence and absence of IFN with A549Luc cells (control cells) and verified that in both cases there was an increase in the amount of luciferase expression upon the addition of IFN, which is concordant with the up-regulation of the IFN… Advisors/Committee Members: Randall, R. E (advisor).

Subjects/Keywords: Virus; Interferon; Antiviral drugs; STAT1; IFN signaling pathway; Cell-based screen assays; Mx1; Hepatitis B core protein; Hepatitis C core protein; Rabies P protein

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

APA (6^th Edition):

Nobre, R. (2009). Viral interferon antagonists and antiviral drugs . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/818

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):

Nobre, Rita. “Viral interferon antagonists and antiviral drugs .” 2009. Thesis, University of St. Andrews. Accessed March 05, 2021. http://hdl.handle.net/10023/818.

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

MLA Handbook (7^th Edition):

Nobre, Rita. “Viral interferon antagonists and antiviral drugs .” 2009. Web. 05 Mar 2021.

Vancouver:

Nobre R. Viral interferon antagonists and antiviral drugs . [Internet] [Thesis]. University of St. Andrews; 2009. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10023/818.

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

Council of Science Editors:

Nobre R. Viral interferon antagonists and antiviral drugs . [Thesis]. University of St. Andrews; 2009. Available from: http://hdl.handle.net/10023/818

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

York University

24. Hassan, Muhammad Murtaza. Synthesis of Novel Cyclobutane Nucleoside Analogues.

Degree: MSc -MS, Chemistry, 2018, York University

URL: http://hdl.handle.net/10315/34283

► A synthesis of cyclobutane nucleosides is described. The method involved the triflation of a -hydroxymethyl-cyclobutanone and its subsequent displacement by a 6-chloropurinyl anion to generate… (more)

Subjects/Keywords: Chemistry; Nucleoside analogues; Antiviral agents; Antitumor agents; Organic chemistry; Cyclobutanone; Cyclobutane; Carboycylic; Photochemistry; Ring-expansion; Reduction; Stereospecific reduction; NMR; Nuclear magnetic resonance spectroscopy; IR; Infrared spectroscopy; UV-Visible; Ultra-violet visible spectroscopy; MS; Mass spectroscopy; Cycloelimination; Decarboxylation; Cyclobutanol; Cyclopropane; Alkene; Furanose; Mitsunobu; N-alkylation; Purine; 6-chloropurine; Pyrimidine; Alcohol; Medicine; Drugs; Photon; Solvents; Chromatography; DNA; RNA; Crystallography; Crystal structure; Biochemistry; Nucleobases; Nitrogenous bases; Nucleic acids; Modifications of nucleosides; Kinases; Suffocation; Triflate; Triflation; Mesylation; Mesylate; Tosylate; Regioisomer; N-9; N-7; Theoretical calculations

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

APA (6^th Edition):

Hassan, M. M. (2018). Synthesis of Novel Cyclobutane Nucleoside Analogues. (Masters Thesis). York University. Retrieved from http://hdl.handle.net/10315/34283

Chicago Manual of Style (16^th Edition):

Hassan, Muhammad Murtaza. “Synthesis of Novel Cyclobutane Nucleoside Analogues.” 2018. Masters Thesis, York University. Accessed March 05, 2021. http://hdl.handle.net/10315/34283.

MLA Handbook (7^th Edition):

Hassan, Muhammad Murtaza. “Synthesis of Novel Cyclobutane Nucleoside Analogues.” 2018. Web. 05 Mar 2021.

Vancouver:

Hassan MM. Synthesis of Novel Cyclobutane Nucleoside Analogues. [Internet] [Masters thesis]. York University; 2018. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10315/34283.

Council of Science Editors:

Hassan MM. Synthesis of Novel Cyclobutane Nucleoside Analogues. [Masters Thesis]. York University; 2018. Available from: http://hdl.handle.net/10315/34283

Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ)

25. Κουμερκερίδης, Γεώργιος. Η συμβολή της βιοτεχνολογίας (αλληλουχία γονιδίων) στον προσδιορισμό των γονοτύπων και στην ανάδειξη μεταλλάξεων του ιού της ηπατίτιδας Β μετά από αντι-ική θεραπεία.

Degree: 2009, Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ)

URL: http://hdl.handle.net/10442/hedi/19488

►

The purpose of the study was to use bi-directional PCR sequencing, in order to detect resistance mutations to lamivudine and adefovir. Using PCR sequencing assay,… (more)

▼

The purpose of the study was to use bi-directional PCR sequencing, in order to detect resistance mutations to lamivudine and adefovir. Using PCR sequencing assay, all mutations in the region of reverse transcriptase of the A-E domains of HBV polymerase could be identified as well as mutations correlated to drug resistance and mutations not correlated to drug resistance. One hundred patients with chronic HBeAg (–) chronic hepatitis B participated in the study and were initially treated with lamivudine. At baseline and every 3 months thereafter, biochemical, aminotransferase levels and viral load were examined. The results of the present study showed that the mean time of resistance to lamivudine treatment was 34.8±17.73 months and that the elevation of viral load from nadir and ALT showed a high deviation among patients with a mean ALT level of 165.5±247.49 and mean HBV DNA 26.3±76.11 (x106 copies /ml). Concerning resistance mutations under the pressure of lamivudine, the following was observed: 3 patients had a mutation in position 180, 66 in 180+204, 30 in 204 and 1 patient in position 173+204. Furthermore, it was found that levels of HBV DNA tended to be a significant marker of resistance time prediction (<0.007), that is lower baseline levels of HBV DNA were correlated with longer time of antiviral resistance to lamivudine treatment (Beta= –0.203). Using the correlation co-efficient, ALT and AST levels were found to have a significant correlation with time of resistance (r=0.621, p<0.0001). Ninety-three/100 patients with resistance to lamivudine were then treated with adefovir as a rescue therapy, in 75 of them adefovir was added to lamivudine and in 11 adefovir was given as monotherapy. In the remaining 9 patients, adefovir and entecavir were given and in 5 more, adefovir was changed to entecavir because of partial response to adefovir. In conclusion, our results showed that genotypic analysis defines the presence of antiviral resistance to the specific drug used for the treatment of chronic hepatitis B, during the time of virologic/biochemical breakthrough, discriminating resistance to partial response to treatment or non-adherence to treatment. Furthermore, our findings support the use of a sensitive assay such as PCR sequencing in detecting both primary and compensatory emerging resistance mutations to the initial therapy so that the drugs used as a rescue therapy do not show cross-resistance or develop multidrug resistance.

Η χρησιμοποίηση μιας ευαίσθητης τεχνικής, της διπλής κατεύθυνσης (bi-directional) PCR sequencing, απετέλεσε και τον σκοπό της παρούσας μελέτης με απώτερο σκοπό την εντόπιση των μεταλλάξεων αντίστασης στη λαμιβουντίνη και την αδεφοβίρη. Με την τεχνική αυτή ήταν δυνατή η ανίχνευση όλων των μεταλλάξεων της περιοχής της ανάστροφης τρανσκρυπτάσης, στις περιοχές Α-Ε της HBV πολυμεράσης. Το υλικό της μελέτης αποτέλεσαν 100 ασθενείς με χρόνια HBeAg(-) ηπατίτιδα Β, οι οποίοι υποβλήθηκαν αρχικά σε θεραπεία με λαμιβουντίνη. Τα ευρήματα της μελέτης έδειξαν ότι ο μέσος χρόνος εμφάνισης αντίστασης…

Subjects/Keywords: Ανάλυση αλληλουχιών γονιδίων; Θεραπεία ηπατίτιδας Β; Νουκλεοσ(Τ)ιδικά φάρμακα; Αντι-ική θεραπεία; Μεταλλάξεις πολυμεράσης ιού Β; Γονότυπος ηπατίτιδας Β; Ηπατίτιδα B (HBV); Μοριακή μέθοδος ιϊκής αντοχής ιού Β; HBV PCR sequencing; Hepatitis B virus (HBV); HBV genotype assay; Nucleos(T)ite drugs; Trugene HBV; Antiviral resistance; HBV polymerase mutations; Hepatitis B, treatment

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

APA (6^th Edition):

Κουμερκερίδης, . �. (2009). Η συμβολή της βιοτεχνολογίας (αλληλουχία γονιδίων) στον προσδιορισμό των γονοτύπων και στην ανάδειξη μεταλλάξεων του ιού της ηπατίτιδας Β μετά από αντι-ική θεραπεία. (Thesis). Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ). Retrieved from http://hdl.handle.net/10442/hedi/19488

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):

Κουμερκερίδης, Γεώργιος. “Η συμβολή της βιοτεχνολογίας (αλληλουχία γονιδίων) στον προσδιορισμό των γονοτύπων και στην ανάδειξη μεταλλάξεων του ιού της ηπατίτιδας Β μετά από αντι-ική θεραπεία.” 2009. Thesis, Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ). Accessed March 05, 2021. http://hdl.handle.net/10442/hedi/19488.

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

MLA Handbook (7^th Edition):

Κουμερκερίδης, Γεώργιος. “Η συμβολή της βιοτεχνολογίας (αλληλουχία γονιδίων) στον προσδιορισμό των γονοτύπων και στην ανάδειξη μεταλλάξεων του ιού της ηπατίτιδας Β μετά από αντι-ική θεραπεία.” 2009. Web. 05 Mar 2021.

Vancouver:

Κουμερκερίδης �. Η συμβολή της βιοτεχνολογίας (αλληλουχία γονιδίων) στον προσδιορισμό των γονοτύπων και στην ανάδειξη μεταλλάξεων του ιού της ηπατίτιδας Β μετά από αντι-ική θεραπεία. [Internet] [Thesis]. Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ); 2009. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10442/hedi/19488.

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

Council of Science Editors:

Κουμερκερίδης �. Η συμβολή της βιοτεχνολογίας (αλληλουχία γονιδίων) στον προσδιορισμό των γονοτύπων και στην ανάδειξη μεταλλάξεων του ιού της ηπατίτιδας Β μετά από αντι-ική θεραπεία. [Thesis]. Aristotle University Of Thessaloniki (AUTH); Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ); 2009. Available from: http://hdl.handle.net/10442/hedi/19488

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

26. Khanna, Mayank. The role of heparan sulfate in poxvirus infections .

Degree: 2015, Australian National University

URL: http://hdl.handle.net/1885/101515

► The heparan sulfate (HS) component of heparan sulfate proteoglycans (HSPGs) has been implicated in the initiation of several viral infections, including vaccinia virus (VACV). A… (more)

▼ The heparan sulfate (HS) component of heparan sulfate proteoglycans (HSPGs) has been implicated in the initiation of several viral infections, including vaccinia virus (VACV). A cell infected with VACV releases two different forms of VACV, namely the mature virus (MV) released following the death of infected cells and which infects neighbouring cells, and the enveloped virus (EV) ejected from infected cells for long-range dissemination. The relative role of HS in the infectivity of the different forms of VACV is unclear. Furthermore, there is little known about the fine specificity of the VACV-HS interactions. Therefore, in order to develop HS based molecules that could potentially have antiviral properties against HS-dependent viral infection, VACV was used as a prototype virus to understand the structural and functional consequences of the interaction between VACV and HS. ELISA studies described in Chapter 3 were used to evaluate the specificity of the MV form of VACV for heparin, differentially sulfated HS, chondroitin sulfate (CS) A-D and hyaluronic acid (HA). Lack of appropriate EV specific antibodies meant that similar ELISA studies could not be performed for the EV form of VACV. Nevertheless, the MV form of VACV bound to immobilized heparin and highly sulfated HS (HShi) with high avidity, compared to lowly sulfated HS (HSlow). The MV particles also bound to CS A-D, however, very weakly. Furthermore, the ability of the MV rich Western Reserve (WR) strain of VACV to form plaques in vitro was affected by soluble heparin, WR plaque numbers being reduced 5-fold with an incremental increase in plaque size. The formation of plaques by the EV rich International Health Department-J (IHD-J) strain was also affected in the presence of heparin, there being a 10-fold reduction in plaque numbers, an incremental increase in plaque size and the disappearance of the trademark ‘comet’ shaped plaques. These data suggest that HS recognition plays a significant role in both MV and EV infectivity, with this recognition being more important for EV infectivity. To better understand the interaction between heparin/HS and the two forms of VACV, green fluorescent protein (GFP) expressing recombinant strains of VACV were constructed, as described in Chapter 4. Subsequent inhibition of infectivity assays, performed using soluble glycosaminoglycans (GAGs), suggested that sulfated GAGs more easily inhibited EV infections than the MV infections, with heparin and HShi being highly potent inhibitors of infection. Furthermore, the ability of the EV form of VACV to establish an infection was significantly reduced in cells treated with the HS-degrading enzyme heparanase and in cells genetically deficient in HS production, compared to the MV form of VACV which appeared largely unaffected. These findings confirmed that recognition of cell surface HS is vital for EV infectivity but less important for the infectivity of the MV form of VACV. In Chapter 5, the ability of soluble heparin/HS molecules and HS mimetics…

Subjects/Keywords: Vaccinia virus (VV or VACV); Western reserve (WR); International Health Department-J (IHD-J); envelope virus (EV or EEV); mature virus (MV or IMV); plaque formation; comets; virus entry; virus exit; virus spread; heparin; heparin chain length; heparin chain linkage; heparan sulphate (HS); heparan sulfate mimetics; glycosaminoglycans (GAGs); extracellular matrix (ECM); antiviral drugs; heparanase; Muparfostat (PI-88)

…antiviral activity into sites of infection, the results obtained from the current study are… …infections are of particular concern as the advances in the field of antiviral drug development… …have lagged behind those of bacteriocidal drugs and antibiotics, especially in the case of… …emerging viral pathogens where the development of antiviral therapies has significantly lagged… …antiviral therapies to counter new infectious diseases. In order to establish an infection, viral…

11 more images…

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

APA (6^th Edition):

Khanna, M. (2015). The role of heparan sulfate in poxvirus infections . (Thesis). Australian National University. Retrieved from http://hdl.handle.net/1885/101515

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):

Khanna, Mayank. “The role of heparan sulfate in poxvirus infections .” 2015. Thesis, Australian National University. Accessed March 05, 2021. http://hdl.handle.net/1885/101515.

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

MLA Handbook (7^th Edition):

Khanna, Mayank. “The role of heparan sulfate in poxvirus infections .” 2015. Web. 05 Mar 2021.

Vancouver:

Khanna M. The role of heparan sulfate in poxvirus infections . [Internet] [Thesis]. Australian National University; 2015. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/1885/101515.

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

Council of Science Editors:

Khanna M. The role of heparan sulfate in poxvirus infections . [Thesis]. Australian National University; 2015. Available from: http://hdl.handle.net/1885/101515

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