Abstract
Human enterovirus A71 (EV-A71) is the major causative agent of hand, foot, and mouth disease (HFMD), which may lead to neurological sequelae and even death. Although EV-A71 seriously threatens public health, there remains no efficient drug for the treatment of EV-A71 infection. We previously demonstrated that ROCK1 is a novel host dependency factor for EV-A71 replication and can serve as a target for the development of anti-EV-A71 therapeutics. In this study, we identified a subset of inhibitors with potential anti-EV-A71 activity by virtual screening using ROCK1 as a target. Among the hits, Dasabuvir, an HCV polymerase inhibitor, was found to have the best antiviral activity which is consistent with the ranking scores in Autodock Vina and iGEMDOCK. We found that Dasabuvir efficiently suppressed EV-A71 replication in a dose-dependent manner. Moreover, Dasabuvir not only efficiently suppressed the replication of EV-A71 in RD cells, but also in multiple cell lines, including HEK-293T, Caco-2, HT-29, HepG2, and Huh7. Besides, Dasabuvir alleviated the release of proinflammatory cytokines caused by EV-A71 infection. Notably, Dasabuvir also exhibited antiviral activity of CVA10, indicating it may have broad-spectrum antiviral activity against species Enteroviruses A. Hence, our results further confirm that ROCK1 can be a potential drug target and suggest Dasabuvir could be a clinical candidate for the treatment of EV-A71 infection.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
