Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Vemurafenib Inhibits Enterovirus A71 Genome Replication and Virus Assembly

Version 1 : Received: 19 July 2022 / Approved: 25 July 2022 / Online: 25 July 2022 (12:25:13 CEST)

How to cite: Hu, B.; Chik, K.K.; Chan, J.F.; Cai, J.; Tsang, J.O.; Zou, Z.; Tang, K.; Jia, L.; Luo, C.; Yin, F.; Ye, Z.; Chu, H.; Yeung, M.; Yuan, S. Vemurafenib Inhibits Enterovirus A71 Genome Replication and Virus Assembly. Preprints 2022, 2022070375 (doi: 10.20944/preprints202207.0375.v1). Hu, B.; Chik, K.K.; Chan, J.F.; Cai, J.; Tsang, J.O.; Zou, Z.; Tang, K.; Jia, L.; Luo, C.; Yin, F.; Ye, Z.; Chu, H.; Yeung, M.; Yuan, S. Vemurafenib Inhibits Enterovirus A71 Genome Replication and Virus Assembly. Preprints 2022, 2022070375 (doi: 10.20944/preprints202207.0375.v1).

Abstract

Enterovirus A71 (EV-A71) infection is a major cause of hand, foot and mouth disease (HFMD) which may be occasionally associated with severe neurological complications. There are currently a lack of treatment options for EV-A71 infection. The Raf-MEK-ERK signaling pathway, in addition to its critical importance in the regulation of cell growth, differentiation and survival, has been shown to be essential for virus replication. In this study, we investigated the anti-EV-A71 activity of vemurafenib, a clinically approved B-Raf inhibitor used in the treatment of late stage melanoma. Vemurafenib exhibits potent anti-EV-A71 effect in cytopathic effect inhibition and viral load reduction assays, with half maximal effective concentration (EC50) at nanomolar concentration. Mechanistically, vemurafenib interrupts both EV-A71 genome replication and assembly. These findings expand the list of potential antiviral candidates of anti-EV-A71 therapeutics.

Keywords

Enterovirus; vemurafenib; RAF; MAPK signaling pathway; genome replication; virus assembly; VP0 cleavage

Subject

LIFE SCIENCES, Virology

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