2. Academic Validation
  3. Hepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease

Hepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease

  • Sci Rep. 2022 Jul 16;12(1):12197. doi: 10.1038/s41598-022-15930-z.
Babak Andi 1 2,  Desigan Kumaran 3 4,  Dale F Kreitler 5,  Alexei S Soares 5,  Jantana Keereetaweep 6,  Jean Jakoncic 5,  Edwin O Lazo 5,  Wuxian Shi 5,  Martin R Fuchs 5,  Robert M Sweet 5,  John Shanklin 6,  Paul D Adams 7 8 9,  Jurgen G Schmidt 10 9,  Martha S Head 11 9,  Sean McSweeney 12 13 14
Affiliations

Affiliations

  • 1 Center for BioMolecular Structure, NSLS-II, Brookhaven National Laboratory, Upton, NY, 11973, USA. bandi@bnl.gov.
  • 2 National Virtual Biotechnology Laboratory (NVBL), US Department of Energy, Washington, DC, USA. bandi@bnl.gov.
  • 3 Biology Department, Brookhaven National Laboratory, Upton, NY, 11973, USA. kumaran@bnl.gov.
  • 4 National Virtual Biotechnology Laboratory (NVBL), US Department of Energy, Washington, DC, USA. kumaran@bnl.gov.
  • 5 Center for BioMolecular Structure, NSLS-II, Brookhaven National Laboratory, Upton, NY, 11973, USA.
  • 6 Biology Department, Brookhaven National Laboratory, Upton, NY, 11973, USA.
  • 7 Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
  • 8 Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.
  • 9 National Virtual Biotechnology Laboratory (NVBL), US Department of Energy, Washington, DC, USA.
  • 10 Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.
  • 11 Joint Institute for Biological Sciences, Oak Ridge National Laboratory, Oak Ridge, TN, 37831, USA.
  • 12 Center for BioMolecular Structure, NSLS-II, Brookhaven National Laboratory, Upton, NY, 11973, USA. smcsweeney@bnl.gov.
  • 13 Biology Department, Brookhaven National Laboratory, Upton, NY, 11973, USA. smcsweeney@bnl.gov.
  • 14 National Virtual Biotechnology Laboratory (NVBL), US Department of Energy, Washington, DC, USA. smcsweeney@bnl.gov.
PMID: 35842458 DOI: 10.1038/s41598-022-15930-z
Abstract

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), threatens global public health. The world needs rapid development of new antivirals and vaccines to control the current pandemic and to control the spread of the variants. Among the proteins synthesized by the SARS-CoV-2 genome, main Protease (Mpro also known as 3CLpro) is a primary drug target, due to its essential role in maturation of the viral polyproteins. In this study, we provide crystallographic evidence, along with some binding assay data, that three clinically approved anti hepatitis C virus drugs and two other drug-like compounds covalently bind to the Mpro Cys145 catalytic residue in the active site. Also, molecular docking studies can provide additional insight for the design of new Antiviral inhibitors for SARS-CoV-2 using these drugs as lead compounds. One might consider derivatives of these lead compounds with higher affinity to the Mpro as potential COVID-19 therapeutics for further testing and possibly clinical trials.

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