Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides

Author:

Wang Bing12ORCID,Svetlov Vladimir3ORCID,Wolf Yuri I.4ORCID,Koonin Eugene V.4ORCID,Nudler Evgeny35,Artsimovitch Irina12ORCID

Affiliation:

1. Department of Microbiology, The Ohio State University, Columbus, Ohio, USA

2. The Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA

3. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA

4. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA

5. Howard Hughes Medical Institute, New York University School of Medicine, New York, New York, USA

Abstract

In vitro interrogations of the central replicative complex of SARS-CoV-2, RNA-dependent RNA polymerase (RdRp), by structural, biochemical, and biophysical methods yielded an unprecedented windfall of information that, in turn, instructs drug development and administration, genomic surveillance, and other aspects of the evolving pandemic response. They also illuminated the vast disparity in the methods used to produce RdRp for experimental work and the hidden impact that this has on enzyme activity and research outcomes.

Funder

National Institute of General Medical Sciences

HHS | NIH | National Institute of General Medical Sciences

Howard Hughes Medical Institute

HHS | NIH | U.S. National Library of Medicine

Blavatnik Family Foundation

Ohio State University

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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