Clofazimine derivatives as potent broad-spectrum antiviral agents with dual-target mechanism.
Eur J Med Chem
; 234: 114209, 2022 Apr 15.
Article
in English
| MEDLINE | ID: covidwho-1719653
ABSTRACT
Thirty-two clofazimine derivatives, of which twenty-two were new, were synthesized and evaluated for their antiviral effects against both rabies virus and pseudo-typed SARS-CoV-2, taking clofazimine (1) as the lead. Among them, compound 15f bearing 4-methoxy-2-pyridyl at the N5-position showed superior or comparable antiviral activities to lead 1, with the EC50 values of 1.45 µM and 14.6 µM and the SI values of 223 and 6.1, respectively. Compound 15f inhibited rabies and SARS-CoV-2 by targeting G or S protein to block membrane fusion, as well as binding to L protein or nsp13 to inhibit intracellular biosynthesis respectively, and thus synergistically exerted a broad-spectrum antiviral effect. The results provided useful scientific data for the development of clofazimine derivatives into a new class of broad-spectrum antiviral candidates.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
COVID-19
Type of study:
Experimental Studies
Limits:
Humans
Language:
English
Journal:
Eur J Med Chem
Year:
2022
Document Type:
Article
Affiliation country:
J.ejmech.2022.114209
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