Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening.
ACS Pharmacol Transl Sci
; 3(5): 1008-1016, 2020 Oct 09.
Article
in English
| MEDLINE | ID: covidwho-872649
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emphasized the urgency to develop effective therapeutics. Drug repurposing screening is regarded as one of the most practical and rapid approaches for the discovery of such therapeutics. The 3C-like protease (3CLpro), or main protease (Mpro) of SARS-CoV-2 is a valid drug target as it is a specific viral enzyme and plays an essential role in viral replication. We performed a quantitative high-throughput screening (qHTS) of 10â¯755 compounds consisting of approved and investigational drugs, and bioactive compounds using a SARS-CoV-2 3CLpro assay. Twenty-three small molecule inhibitors of SARS-CoV-2 3CLpro have been identified with IC50s ranging from 0.26 to 28.85 µM. Walrycin B (IC50 = 0.26 µM), hydroxocobalamin (IC50 = 3.29 µM), suramin sodium (IC50 = 6.5 µM), Z-DEVD-FMK (IC50 = 6.81 µM), LLL-12 (IC50 = 9.84 µM), and Z-FA-FMK (IC50 = 11.39 µM) are the most potent 3CLpro inhibitors. The activity of the anti-SARS-CoV-2 viral infection was confirmed in 7 of 23 compounds using a SARS-CoV-2 cytopathic effect assay. The results demonstrated a set of SARS-CoV-2 3CLpro inhibitors that may have potential for further clinical evaluation as part of drug combination therapies to treating COVID-19 patients and as starting points for chemistry optimization for new drug development.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
/
Prognostic study
Language:
English
Journal:
ACS Pharmacol Transl Sci
Year:
2020
Document Type:
Article
Affiliation country:
Acsptsci.0c00108
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