Design,Synthesis And Activity Study Of New Anti-EV71 Virus 3C Protease Inhibitors

The enterovirus 71 is the major pathogens of HFMD.It has become an important infectious disease threaten children’s health.But there are still lacking of effective EV71 vaccine and anti-EV71 drug.In this study,Our group choses Rupintrivir()which is EV71 3C protease inhibitor as the leading compound.Though virtual screening(Mopac2007)and molecular docking(Molegro Virtual Docker),we designed and synthesised four new peptides by solid-phase strategy.Those peptides are H2N-Val-Trp-Phe-His-Phe-OH(compound 25)、H2N-His-Trp-Phe-His-Phe-OH(compound 35)、H2N-Ala-Trp-Phe-Lys-Cys-OH(compound43)、H2N-Pro-Phe-Trp-Phe-Ala-OH(compound 16).The purity of four peptides are more than 95%by HPLC,and the structure was confirmed by ESI-MS.We chose human muscle tumor cell lines which is easy to infect EV71 as preliminary activity screening model,we found that the compound 25 and the compound 16 have the anti-EV71 activity by method of Western Blot and RT-PCR.The results show compound 25 can inhibit the EV71 3C protease(IE50=1μg·ml-1 CC50=155.73μg·ml-1,SI=155.73),but the anti-EV71 virus activity of compound 16 is poor.So,compound 25 can be further used as a lead compound to research.