High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors.
Protein Cell
; 14(1): 17-27, 2023 01.
Article
in English
| MEDLINE | ID: covidwho-2222718
ABSTRACT
The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Protease Inhibitors
/
SARS-CoV-2
/
COVID-19
Type of study:
Diagnostic study
/
Screening_studies
Limits:
Humans
Language:
English
Journal:
Protein Cell
Journal subject:
Biochemistry
Year:
2023
Document Type:
Article
Affiliation country:
Procel
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