Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2.
ACS Med Chem Lett
; 11(12): 2526-2533, 2020 Dec 10.
Article
in English
| MEDLINE | ID: covidwho-889131
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
A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with Mpro, 17 were chosen for evaluation in a kinetic assay for Mpro inhibition. Remarkably 14 of the compounds at 100-µM concentration were found to reduce the enzymatic activity and 5 provided IC50 values below 40 µM manidipine (4.8 µM), boceprevir (5.4 µM), lercanidipine (16.2 µM), bedaquiline (18.7 µM), and efonidipine (38.5 µM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1', and P2 pockets of Mpro. Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
/
Prognostic study
Language:
English
Journal:
ACS Med Chem Lett
Year:
2020
Document Type:
Article
Affiliation country:
Acsmedchemlett.0c00521
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