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DOI: 10.1055/a-1582-0243
De novo Design of SARS-CoV-2 Main Protease Inhibitors
D.T. and his group are thankful for the COVID-19 Catalyst Grant by the New York University (NYU). Y.Z. would like to acknowledge the support by the National Institutes of Health (NIH, Grant No. R35 GM127040). C.F. thanks the Swiss National Science Foundation (SNSF, Grant No. 178569) for a postdoctoral fellowship. N.A.V. thanks the Studienstiftung des Deutschen Volkes (German Academic Scholarship Foundation) for a PhD Fellowship. Z.P. and K.P.R. are supported by the New York University (NYU) MacCracken Fellowship.


Abstract
The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, MPro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.
Key words
viral main protease - small-molecule inhibitor - SARS-CoV-2 - coronavirus - molecular modelingSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1582-0243.
- Supporting Information
Publication History
Received: 13 July 2021
Accepted after revision: 10 August 2021
Accepted Manuscript online:
10 August 2021
Article published online:
05 October 2021
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