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

View ORCID ProfileDavid N. Frick, Rajdeep S. Virdi, Nemanja Vuksanovic, Narayan Dahal, Nicholas R. Silvaggi
doi: https://doi.org/10.1101/2020.03.31.014639
David N. Frick
1Departments of Chemistry & Biochemistry, The University of Wisconsin-Milwaukee, Milwaukee, WI 53217
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  • For correspondence: frickd@uwm.edu
Rajdeep S. Virdi
1Departments of Chemistry & Biochemistry, The University of Wisconsin-Milwaukee, Milwaukee, WI 53217
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Nemanja Vuksanovic
1Departments of Chemistry & Biochemistry, The University of Wisconsin-Milwaukee, Milwaukee, WI 53217
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Narayan Dahal
2Physics, The University of Wisconsin-Milwaukee, Milwaukee, WI 53217
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Nicholas R. Silvaggi
1Departments of Chemistry & Biochemistry, The University of Wisconsin-Milwaukee, Milwaukee, WI 53217
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ABSTRACT

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

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Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 29, 2020.
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Molecular Basis for ADP-ribose Binding to the Macro-X Domain of SARS-CoV-2 Nsp3
David N. Frick, Rajdeep S. Virdi, Nemanja Vuksanovic, Narayan Dahal, Nicholas R. Silvaggi
bioRxiv 2020.03.31.014639; doi: https://doi.org/10.1101/2020.03.31.014639
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Molecular Basis for ADP-ribose Binding to the Macro-X Domain of SARS-CoV-2 Nsp3
David N. Frick, Rajdeep S. Virdi, Nemanja Vuksanovic, Narayan Dahal, Nicholas R. Silvaggi
bioRxiv 2020.03.31.014639; doi: https://doi.org/10.1101/2020.03.31.014639

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