Repurposing Low-Molecular-Weight Drugs against the Main Protease of Severe Acute Respiratory Syndrome Coronavirus 2.
J Phys Chem Lett
; 11(17): 7267-7272, 2020 Sep 03.
Article
in English
| MEDLINE | ID: covidwho-678527
ABSTRACT
The coronavirus disease pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease (Mpro) of SARS-CoV-2, thereby modestly inhibiting the enzymatic activity of Mpro. We further searched for low-molecular-weight drugs containing niacin or hit 1 pharmacophores with enhanced inhibiting activity, e.g., carmofur, bendamustine, triclabendazole, emedastine, and omeprazole, in which omeprazole is the only one binding to the C-terminal domain of SARS-CoV-2 Mpro. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Peptide Hydrolases
/
Drug Repositioning
/
Betacoronavirus
Language:
English
Journal:
J Phys Chem Lett
Year:
2020
Document Type:
Article
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