Dissertation > Medicine, health > Pharmacy > Pharmacology > Molecular Pharmacology

The Research on Pharmacodynamics and Mechanism of Anti-influenza a Virus Drugs

Author LiMengZuo
Tutor ZengYi
School Beijing University of Technology
Course Biochemistry and Molecular Biology
Keywords Influenza A virus Antiviral drug Nucleoprotein Synergistic effect Molecular docking
CLC R966
Type Master's thesis
Year 2013
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Influenza A viruses mutate easily, so they are common and have strong virulence.Human beings cannot obtain lasting immunity. However, anti-influenza A drugs usedin clinic limit to two main classes which are the ion channel blocker and the viralneuraminidase inhibitors. Some virus strains have shown drug resistance in someareas. Nucleoprotein plays an important role in genome replication, and its antigenstructure is very stable, so nucleoprotein can be an ideal drug target. There is no drugaimed to nucleoprotein in clinic in the world.In this reseach we chose nucleoprotein (NP) as the main target combining withmembrane proteins (HA、 NA) aimed to research multiple targets drugs.Thecompounds of KA series were natural compounds and all had a similar mothernucleus.Among them, KA30was a product from KA20which molecular structureadded polar groups. By use of Biacore SPR test, it shown that KA30had goodbinding ability with NP,and KA60-3had good binding ability with HA and NP atmolecular level. By use of ELISA test, it shown that KA20, KA30, KA60-1, KA60-2,KA60-3and KA60-4had good inhibitory effect on H1N1at cellular level. Theinhibitory effect of structure optimizing KA30was stronger than KA20. In addition,we found that KA30, KA60-1, KA60-3and KA60-7had inhibitory effect on NA byuse of Neuraminidase Inhibitors Screen Kit.The third generation of drug combination method combines MacSynergyⅡsoftware with ELISA method, which can research synergy effect between differentdrugs. It shown that KA30produced synergistic effect respectively with LianhuaQingwen capsules, Shanxiangyuan tablets and tamiflu(oseltamivir).Both tamiflu andLianhua Qingwen capsules were synergistic with Shanxiangyuan tablets.Using bioinformatics software Discovery Studio2.5to simulate moleculardocking and research the mechanism of KA30. The results shown that KA30has goodbinding ability with NA and NP. Both KA30and KA20had similar bonding styles.The libdock scores of KA30were slightly higher than KA20at some same sites.Itshowed that the structure of KA30was optimizing.

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