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The Study on Anti-Vral Mechanism of Compounds Derived from Marine Organisms

Author: ZhangWenJun
Tutor: ZengYi; LiZeLin
School: Beijing University of Technology
Course: Biochemistry and Molecular Biology
Keywords: HIV-1 H1N1 Vif APOBEC3G Neuraminidase
CLC: R285
Type: Master's thesis
Year: 2012
Downloads: 63
Quote: 0
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Abstract


The acquired immunodeficiency syndrome (AIDS), mainly caused by HIV-1, hasbecame a serious threat to human health since1981. Although antiviral therapy hasimproved by Reverse Transcriptase Inhibitors of highly active antiretroviral therapy(HAART) during the last two decades, the viral resistance and the toxicity associatedwith these inhibitors suggest that there is a need to develop more potent and saferones. Human APOBEC3G is a host inhibitor of HIV-1. The bind of HIV-1Vif to A3Gcan cause the degradation of A3G with the help of CBF-beta. Therefore, the researchabout the inhibitors targeting A3G-Vif has became a hotspot for the development ofanti-HIV-1drugs.In the study, a screening system was established to discover the inhibitors thatprotected the degradation of A3G by Vif, and nine small compounds were identifiedwith this system. The pharmacokinetics evaluation of these anti-HIV-1molecules wasfinished, and the relationships of their structure and efficacy were analyzed with themethods of Co-transfection and Molecule docking. The results demonstrated that theHIV-1Vif-A3G axis was a valid target for the development of anti-HIV-1drugs.New-type H1N1has been a major threat to human health since2009of the flupandemic. Although Tamiflu was approved by FDA, it is urgent to develop newinhibitor against the H1N1because of the resistances of virus and the high price. Inthis work, we aimed to identify new inhibitors against H1N1from the extracts ofalligator blood. We established a method of ELISA-based pharmacokineticsevaluation to screen the compounds from the extracts of alligator blood, and foundthat KA40-1, KA40-2and KA40-3had the anti-H1N1activities. Neuraminidasetesting assay showed that KA40-2could inhibit the activity of neuraminidase whereasKA40-1and KA40-3had no effects on neuraminidase.

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