1. Design, synthesis and biological evaluation of betulinic acid derivatives as potential inhibitors of 3CL-protease of SARS-CoV-2.
- Author
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Liu Y, Nie T, Hou J, Long H, Zhang Z, Lei M, Xu Y, and Wu W
- Subjects
- Humans, Peptide Hydrolases, Betulinic Acid, Antiviral Agents chemistry, SARS-CoV-2, COVID-19
- Abstract
During the coronavirus reproduction process, 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are accountable for the fragmentation of two polyprotein precursors (pp1a/pp1ab) into substructural proteins. These two proteins are vital for the replication and transcription of the viral genome. Therefore, 3CLpro is a key protein and target for the design of coronavirus inhibitors. In previous studies, we found that betulinic acid has an inhibitory effect on 3CLpro, with 51.5 % inhibition of 3CLpro at 20 µM. Then, series of betulinic acid derivatives were designed, synthesized, and evaluated for their inhibition activities. The results showed that BA02 and BA05 showed significant inhibitory activity on 3CLpro with inhibitory rates of 78.1 % and 82.5 % at 20 µM, respectively. Further evaluation of these two compounds shows that their IC
50 values are 7.22 ± 0.14 μM and 6.40 ± 0.14 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)- Published
- 2024
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