jm7b00103_si_001.pdf (5.55 MB)
Michael Acceptor-Based Peptidomimetic Inhibitor of Main Protease from Porcine Epidemic Diarrhea Virus
journal contribution
posted on 2017-03-13, 00:00 authored by Fenghua Wang, Cheng Chen, Kailin Yang, Yang Xu, Xiaomei Liu, Fan Gao, He Liu, Xia Chen, Qi Zhao, Xiang Liu, Yan Cai, Haitao YangPorcine epidemic
diarrhea virus (PEDV) causes high mortality in
pigs. PEDV main protease (Mpro) plays an essential role
in viral replication. We solved the structure of PEDV Mpro complexed with peptidomimetic inhibitor N3 carrying a Michael acceptor
warhead, revealing atomic level interactions. We further designed
a series of 17 inhibitors with altered side groups. Inhibitors M2
and M17 demonstrated enhanced specificity against PEDV Mpro. These compounds have potential as future therapeutics to combat
PEDV infection.