Discovery of potent benzoxaborole inhibitors against SARS-CoV-2 main and dengue virus proteases.
Eur J Med Chem
; 240: 114585, 2022 Oct 05.
Article
in English
| MEDLINE | ID: covidwho-1982958
ABSTRACT
The RNA viruses SARS-CoV-2 and dengue pose a major threat to human health worldwide and their proteases (Mpro; NS2B/NS3) are considered as promising targets for drug development. We present the synthesis and biological evaluation of novel benzoxaborole inhibitors of these two proteases. The most active compound achieves single-digit micromolar activity against SARS-CoV-2 Mpro in a biochemical assay. The most active substance against dengue NS2B/NS3 protease has submicromolar activity in cells (EC50 0.54 µM) and inhibits DENV-2 replication in cell culture. Most benzoxaboroles had no relevant cytotoxicity or significant off-target inhibition. Furthermore, the class demonstrated passive membrane penetration and stability against the evaluated proteases. This compound class may contribute to the development of antiviral agents with activity against DENV or SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Dengue
/
Dengue Virus
/
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.2022.114585
Similar
MEDLINE
...
LILACS
LIS