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Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Non-Covalent Inhibitor ML188
- Source :
- Viruses, Vol 13, Iss 2, p 174 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 is in dire need of DAAs. The Main protease (Mpro) is the focus of extensive structure-based drug design efforts which are mostly covalent inhibitors targeting the catalytic cysteine. ML188 is a non-covalent inhibitor designed to target SARS-CoV-1 Mpro, and provides an initial scaffold for the creation of effective pan-coronavirus inhibitors. In the current study, we found that ML188 inhibits SARS-CoV-2 Mpro at 2.5 µM, which is more potent than against SAR-CoV-1 Mpro. We determined the crystal structure of ML188 in complex with SARS-CoV-2 Mpro to 2.39 Å resolution. Sharing 96% sequence identity, structural comparison of the two complexes only shows subtle differences. Non-covalent protease inhibitors complement the design of covalent inhibitors against SARS-CoV-2 main protease and are critical initial steps in the design of DAAs to treat CoVID 19.
- Subjects :
- SARS-CoV-2
Covid-19
main protease
Mpro
ML188
protease inhibitor
Microbiology
QR1-502
Subjects
Details
- Language :
- English
- ISSN :
- 19994915
- Volume :
- 13
- Issue :
- 2
- Database :
- Directory of Open Access Journals
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5f63463719c241c3bb92df5389254837
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/v13020174