Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2.
Science
; 373(6557): 931-936, 2021 08 20.
Article
in English
| MEDLINE | ID: covidwho-1319369
ABSTRACT
There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a human beta coronavirus that causes the common cold, and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in cultured human cells. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray crystallography and biochemistry show that masitinib acts as a competitive inhibitor of 3CLpro. Mice infected with SARS-CoV-2 and then treated with masitinib showed >200-fold reduction in viral titers in the lungs and nose, as well as reduced lung inflammation. Masitinib was also effective in vitro against all tested variants of concern (B.1.1.7, B.1.351, and P.1).
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Thiazoles
/
Cysteine Proteinase Inhibitors
/
Coronavirus OC43, Human
/
Coronavirus 3C Proteases
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Science
Year:
2021
Document Type:
Article
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