Molecular Basis for ADP-ribose Binding to the Macro-X Domain of SARS-CoV-2 Nsp3

The virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous pro-teins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymers, helicase and main protease, are well con-served between SARS-CoV-2 and the original SARS virus...

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Bibliographic Details
Published inbioRxiv
Main Authors Frick, David, Virdi, Rajdeep S, Vuksanovic, Nemanja, Dahal, Narayan, Silvaggi, Nicholas R
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 29.04.2020
Subjects
Antiviral agents
Coronaviridae
Coronaviruses
COVID-19
DNA helicase
Drug development
Genomes
Ribonucleic acid
Ribose
RNA
RNA helicase
Severe acute respiratory syndrome coronavirus 2
Therapeutic applications
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Summary:The virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous pro-teins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymers, helicase and main protease, are well con-served between SARS-CoV-2 and the original SARS virus, but several others are not. This study examines one of the proteins encoded by SARS-CoV-2 that is most different, a macrodomain of nonstructural protein 3 (nsp3). Although 26% of the amino acids in this SARS-CoV-2 macrodomain differ from those seen in other coronaviruses, bio-chemical and structural data reveal that the protein retains the ability to bind ADP-ribose, which is an important characteristic of beta coronaviruses, and potential therapeutic target. Competing Interest Statement The authors have declared no competing interest. Footnotes * New, more descriptive title, and minor changes in grammar and style.
DOI:10.1101/2020.03.31.014639