Thesis (M. Sc.)--York University, 2007. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 92-98). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004 & res_dat=xri:pqdiss & rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation & rft_dat=xri:pqdiss:MR32030.

Thesis (Ph. D.)--School of Chemistry and Biochemistry, Georgia Institute of Technology, 2004. Directed by Katherine L. Seley. / Includes bibliographical references (leaves 113-126).

Continually reported human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection create heightened threat to public health, due to the disease severity and high lethality. Acute respiratory syndrome (ARDS) has been found to be the most severe form of acute lung injury caused by H5N1 virus infection. Studies have highlighted that the unusually high virulence of H5N1 virus infection is associated with the cytokine dysregulation and enhanced viral replication in the host. In reference to the past experience during Spanish 1918 influenza pandemic and SARS, it is crucial that a novel therapeutic target is explored and employed in time for the effective control of emerging diseases. The pandemic potential of H5N1 influenza virus urges well preparedness not only in terms of containment measures, but also in the treatment aspect of the severe human H5N1 disease. To date, therapeutic approaches are limited to the use of vaccine, antiviral drugs and corticosteroids. It has been suggested that commercially available antiviral drugs are prone to induce resistance mutations; and are effective in the protection against influenza virus infection only if administered during the early course of disease development. Moreover, vaccine development does not grant a promising therapeutic strategy at the time of a pandemic as it takes time for the development and distribution of safe and reliable vaccine. In attempts to search for a novel adjunctive therapy in addition to currently available agents, indirubin-3’-oxime (IDO) and indirubin derivative, E804 have been tested to show the effect in cytokine suppression and antiviral activity against H5N1 influenza virus infection in vitro. These compounds have been extracted and purified from a natural herb called Isatis tinctoria which is frequently used for herbal remedy in treating respiratory symptoms in traditional Chinese medicine. In this study, it was demonstrated that IDO and E804 treatment in H5N1 influenza virus infected human alveolar epithelial cells effectively inhibit the proinflammatory cytokine induction and viral replication. This physiologically relevant in vitro alveolar epithelial cell model and the efficacy of IDO and E804 provide new insights to the development of new treatment option for severe human H5N1 disease. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

The goal of this research is to identify a compound or family of compounds that would allow effective treatment of the influenza virus without unnecessary risks and side-effects. Influenza is a substantial problem in today’s society. Each year 36,000 people die in the United States due to influenza, or influenza related causes. Influenza is caused by two types of the virus, Type-A and Type-B. There are currently four FDA approved drugs to treat influenza—two are proton channel blockers and two are neuraminidase inhibitors. The goal of my research was to design a new drug that would allow physicians to effectively treat Type-A and Type-B influenza virus without having their patients endure unnecessary risks and side-effects. Density functional theory calculations were used to optimize the geometries of the ligands. Using sophisticated resources such as the Protein Data Bank and AutoDock, a library of twenty five ligands were docked into the N4 protein. Each docking was performed five times, resulting in one overall average docked energy. The averaged energies for each of the ligands were ranked from lowest to highest. Based upon a different study, one of my ligands were shown to have antiviral activity. From the docked energy for the ligand with confirmed antiviral activity, the results of the highest ranking ligand could be determined to have promising antiviral activity. The ligand shown below is the promising ligand, which will undergo further alterations and dockings to attempt to improve the antiviral activity. / Department of Chemistry

<p>Nevirapine (NVP) is a cheap anti-retroviral drug used in poor countries worldwide, administered to pregnant women at the onset of labour to inhibit HIV enzyme reverse transcriptase. Viruses which may get transmitted to newborns are deficient in this enzyme, and HIV-1 infection cannot be established, thereby preventing mother to child transmission (MTCT). In some cases, babies get infected and positive selection for viruses resistant to nevirapine may be inferred. Positive selection can be inferred from sequence data, when the rate of nonsynonymous substitutions is significantly greater than the rate of synonymous substitutions.</p> <p>Unfortunately, it is found that available positive selection methods should not be used to analyse before- and after- NVP treatment sequence pairs associated with MTCT. Methods which use phylogenetic trees to infer positive selection trace synonymous and nonsynonymous substitutions further back in time than the short time duration during which selection for NVP occurred. The other group of methods for inferring positive selection, the pairwise methods, do not have appreciable power, because they average susbtituion rates over all codons in a sequence pair and not just at single codons. We introduce a simple counting method which we call the Pairwise Homologous Codons (PHoCs) method with which we have inferred positive selection resulting from NVP treatment in longitudinal HIV-1 reverse transcriptase sequences. The PHoCs method estimates rates of substitutions between before- and after- NVP treatment codons, using a simple pairwise method.</p>

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 194-237) Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Also available in print.

Thesis (Ph. D.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 86-100). Also available on the World Wide Web.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 157-186). Also available in print.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1988. / Extra t.p. with thesis statement inserted. Includes bibliographical references.