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.

Details

Title
Hepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease
Author
Andi, Babak 1 ; Kumaran, Desigan 2 ; Kreitler, Dale F. 3 ; Soares, Alexei S. 3 ; Keereetaweep, Jantana 4 ; Jakoncic, Jean 3 ; Lazo, Edwin O. 3 ; Shi, Wuxian 3 ; Fuchs, Martin R. 3 ; Sweet, Robert M. 3 ; Shanklin, John 4 ; Adams, Paul D. 5 ; Schmidt, Jurgen G. 6 ; Head, Martha S. 7 ; McSweeney, Sean 8 

 Brookhaven National Laboratory, Center for BioMolecular Structure, NSLS-II, Upton, USA (GRID:grid.202665.5) (ISNI:0000 0001 2188 4229); US Department of Energy, National Virtual Biotechnology Laboratory (NVBL), Washington, USA (GRID:grid.85084.31) (ISNI:0000000123423717) 
 Brookhaven National Laboratory, Biology Department, Upton, USA (GRID:grid.202665.5) (ISNI:0000 0001 2188 4229); US Department of Energy, National Virtual Biotechnology Laboratory (NVBL), Washington, USA (GRID:grid.85084.31) (ISNI:0000000123423717) 
 Brookhaven National Laboratory, Center for BioMolecular Structure, NSLS-II, Upton, USA (GRID:grid.202665.5) (ISNI:0000 0001 2188 4229) 
 Brookhaven National Laboratory, Biology Department, Upton, USA (GRID:grid.202665.5) (ISNI:0000 0001 2188 4229) 
 Lawrence Berkeley National Laboratory, Molecular Biophysics and Integrated Bioimaging Division, Berkeley, USA (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551); University of California, Department of Bioengineering, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); US Department of Energy, National Virtual Biotechnology Laboratory (NVBL), Washington, USA (GRID:grid.85084.31) (ISNI:0000000123423717) 
 Los Alamos National Laboratory, Bioscience Division, Los Alamos, USA (GRID:grid.148313.c) (ISNI:0000 0004 0428 3079); US Department of Energy, National Virtual Biotechnology Laboratory (NVBL), Washington, USA (GRID:grid.85084.31) (ISNI:0000000123423717) 
 Oak Ridge National Laboratory, Joint Institute for Biological Sciences, Oak Ridge, USA (GRID:grid.135519.a) (ISNI:0000 0004 0446 2659); US Department of Energy, National Virtual Biotechnology Laboratory (NVBL), Washington, USA (GRID:grid.85084.31) (ISNI:0000000123423717) 
 Brookhaven National Laboratory, Center for BioMolecular Structure, NSLS-II, Upton, USA (GRID:grid.202665.5) (ISNI:0000 0001 2188 4229); Brookhaven National Laboratory, Biology Department, Upton, USA (GRID:grid.202665.5) (ISNI:0000 0001 2188 4229); US Department of Energy, National Virtual Biotechnology Laboratory (NVBL), Washington, USA (GRID:grid.85084.31) (ISNI:0000000123423717) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2690369263
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.