Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Wei Ye; Min Yao; Yangchao Dong; Chuantao Ye; Dan Wang; He Liu; Hongwei Ma; Hui Zhang; Libin Qi; Yuewu Yang; Yuan Wang; Liang Zhang; Linfeng Cheng; Xin Lv; Zhikai Xu; Yingfeng Lei; Fanglin Zhang

doi:10.3389/fmicb.2020.01105

Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition

Front Microbiol. 2020 Jun 12:11:1105. doi: 10.3389/fmicb.2020.01105. eCollection 2020.

Authors

Wei Ye¹, Min Yao¹, Yangchao Dong¹, Chuantao Ye², Dan Wang³, He Liu¹, Hongwei Ma¹, Hui Zhang¹, Libin Qi⁴, Yuewu Yang⁴, Yuan Wang¹, Liang Zhang¹, Linfeng Cheng¹, Xin Lv¹, Zhikai Xu¹, Yingfeng Lei¹, Fanglin Zhang¹

Affiliations

¹ Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi'an, China.
² Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
³ Second Affiliated Hospital, Xi'an Medical University, Xi'an, China.
⁴ Cadet Brigade, School of Preclinical Medicine, Fourth Military Medical University, Xi'an, China.

Abstract

Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviruses and indicate that remdesivir is a promising antiviral treatment for EV71 and other enterovirus infections.

Keywords: EV71; Remdesivir (GS-5734); antivirals; cRNA; enterovirus; vRNA.