RESEARCH ARTICLE
Molecular interactions and inhibition of the SARS-CoV-2 main protease by a thiadiazolidinone derivative
Jacob Andrzejczyk,
Katarina Jovic,
Logan M. Brown,
Valerie G. Pascetta,
Krisztina Varga,
Harish Vashisth,
Jacob Andrzejczyk
Department of Chemical Engineering, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorKatarina Jovic
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorLogan M. Brown
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorValerie G. Pascetta
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorKrisztina Varga
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorCorresponding Author
Harish Vashisth
Department of Chemical Engineering, University of New Hampshire, Durham, New Hampshire, USA
Correspondence
Harish Vashisth, Department of Chemical Engineering, University of New Hampshire, Durham, NH 03824, USA.
Email: [email protected]
Search for more papers by this authorJacob Andrzejczyk,
Katarina Jovic,
Logan M. Brown,
Valerie G. Pascetta,
Krisztina Varga,
Harish Vashisth,
Jacob Andrzejczyk
Department of Chemical Engineering, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorKatarina Jovic
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorLogan M. Brown
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorValerie G. Pascetta
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorKrisztina Varga
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA
Search for more papers by this authorCorresponding Author
Harish Vashisth
Department of Chemical Engineering, University of New Hampshire, Durham, New Hampshire, USA
Correspondence
Harish Vashisth, Department of Chemical Engineering, University of New Hampshire, Durham, NH 03824, USA.
Email: [email protected]
Search for more papers by this authorFunding information: National Institutes of Health, Grant/Award Numbers: R35GM138217, P20GM113131; National Science Foundation, Grant/Award Number: OIA-1757371
Abstract
We report molecular interactions and inhibition of the main protease (MPro) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of MPro via docking protocols and molecular dynamics simulations in all-atom detail. We reveal the local and global dynamics of MPro in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC50 value of 1.39 ± 0.22 μM, which is comparable to other known inhibitors of this enzyme.
CONFLICTS OF INTEREST
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are available in the supplementary material of this article
Supporting Information
| Filename | Description |
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| prot26385-sup-0001-supinfo.pdfPDF document, 2.5 MB | Appendix S1 Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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