Efficient Strategy to Design Protease Inhibitors: Application to Enterovirus 71 2A Protease.

ABSTRACT: One strategy to counter viruses that persistently cause outbreaks is to design molecules that can specifically inhibit an essential multifunctional viral protease. Herein, we present such a strategy using well-established methods to first identify a region present only in viral (but not human) proteases and find peptides that can bind specifically to this "unique" region by maximizing the protease-peptide binding free energy iteratively using single-point mutations starting with the substrate peptide. We applied this strategy to discover pseudosubstrate peptide inhibitors for the multifunctional 2A protease of enterovirus 71 (EV71), a key causative pathogen for hand-foot-and-mouth disease affecting young children, along with coxsackievirus A16. Four peptide candidates predicted to b

SUBMITTER: Chen T 

PROVIDER: S-EPMC10125330 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature