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

• Published in: bioRxiv
• Main Authors: Frick, David, Virdi, Rajdeep S, Vuksanovic, Nemanja, Dahal, Narayan, Silvaggi, Nicholas R
• Format: Paper
• Language: English
• 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
• DOI: 10.1101/2020.03.31.014639

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.