新藥設(shè)計與合成全英文匯報

1、Effects of polyphenol compounds on influenza A virus replication and definition of their mechanism of action（一）（一）Background（二）（二）Content（三）（三）Discussion and ConclusionOutlineThe sturcture of influenza viruses Influenza is a majorin fectious disease of humans and animals causing significant morbidit

2、y and mortality worldwide.BackgroundRef: J. Proteome Res. 2011, 10, 34503459.Background Influenza viruses are typed into three categories (A, B, C). According to differences in viral matrix (M) proteins and nucleoproteins. Influenza A, r e s p o n s i b l e f o r m o s t flurelated deaths, is furthe

3、r subtyped according to the antigenic characteristics of the hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins. Ref: Analyical chemistry, 2006, 11(1):7910-7915.On the Types of influenza viruses influenza A viruses (IAV) While type B influenza is almost exclusively a human pathogen, typ

4、e A influenza also infects birds and other mammals.BackgroundCurcumin Curcumin is a colouring compound present in the rhizome of Curcuma longa. It shows many pharmacological properties including antioxid anti-inflammatory and some other activities. Recently, curcumin has been proven to exert anti-in

5、fluenza activity by inhibition of the virus-cell attachment.Ref：Bioorg Med Chem. 2012,12:5046-5052.ContentResveratrol (RV) RV is a very interesting polyphenol belonging to the stilbene family.A few years ago, we showed that RV inhibits influenza virus replication in vitro and in vivo. Surprisingly,

6、these effects are not related to its well-known antioxidant activity. Ref：Bioorg Med Chem. 2012,12:5046-5052.ContentThe polyphenol compoundsContentInhibit late phases of influenza viruslife-cycle These data indicate that the antiviral activity of the compounds is largely related to their inhibition

7、of virus life-cycle steps occurring 2-8 h, and possibly related to post-transcriptional events.ContentCompound 4 inhibits expression of late viral proteins These results suggest that the antiviral activity exerted by 4 could be due to an interference with viral protein synthesis, while the effect of

8、 6g to the inhi-bition of other steps of virus life-cycle.ContentCompounds 6g and 4 retain viral NP in the nucleus of infected cells In the untreated cells, NP was located predominantly in the cytosol, and addition of compounds 4 and 6g led to the inhibition of viral RNP export from nucleus to cytop

9、lasmContentCompounds 6g and 4 retain viral NP in the nucleus of infected cellsContent Discussion (1)These compounds inhibited the influ-enza A virus replication in a dose-dependent manner without inducing any cytotoxic effect (2)The antiviral activity of these molecules is due to inhibition of two key steps of influenza virus life-cycle: a:nuclear-cytoplasmic traffic of vRNP; b: maturation of viral HA protein.Discussion and ConclusionConclusion Overall the data demonstrated that the com