Etoposide targets 2A protease to inhibit enterovirus 71 replication

Abstract

We first used a drug screening approach focused on monomeric compounds and their derivatives from traditional Chinese medicine to identify an EV71 2A pro inhibitor—Etoposide. We then performed biological experiments to validate that Etoposide suppresses the replication of the EV71 virus in a concentration-dependent manner with minimal cytotoxicity to various cell lines. Remarkably, it shows inhibitory activity against EV71 A, B, C, and CVA16, suggesting that Etoposide may be a potential broad-spectrum inhibitor. We revealed a novel mechanism that Etoposide inhibits EV71 proliferation by targeting 2A pro , and the interactions with Y89 and P107 are of great importance. The findings suggest that Etoposide serves as a promising inhibitor of EV71 2A pro , demonstrating significant antiviral properties. It stands out as a strong candidate for broad-spectrum applications in clinical research.