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

Frontiers in Microbiology (Jun 2020)

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

Affiliations

Wei Ye: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Min Yao: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Yangchao Dong: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Chuantao Ye: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
Dan Wang: Second Affiliated Hospital, Xi’an Medical University, Xi’an, China
He Liu: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Hongwei Ma: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Hui Zhang: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Libin Qi: Cadet Brigade, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Yuewu Yang: Cadet Brigade, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Yuan Wang: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Liang Zhang: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Linfeng Cheng: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Xin Lv: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Zhikai Xu: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Yingfeng Lei: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China
Fanglin Zhang: Department of Microbiology, School of Preclinical Medicine, Fourth Military Medical University, Xi’an, China

DOI: https://doi.org/10.3389/fmicb.2020.01105
Journal volume & issue: Vol. 11

Abstract

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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.

Published in Frontiers in Microbiology

ISSN: 1664-302X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.frontiersin.org/journals/microbiology

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