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- Title
Ginkgolic acid and anacardic acid are specific covalent inhibitors of SARS-CoV-2 cysteine proteases.
- Authors
Chen, Zinuo; Cui, Qinghua; Cooper, Laura; Zhang, Pin; Lee, Hyun; Chen, Zhaoyu; Wang, Yanyan; Liu, Xiaoyun; Rong, Lijun; Du, Ruikun
- Abstract
Background: In the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds. Results: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) in addition to PLpro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CLpro and PLpro. Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations. Conclusions: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.
- Subjects
CYSTEINE proteinases; SARS-CoV-2; ENZYME kinetics; NATURAL products; LEAD compounds
- Publication
Cell & Bioscience, 2021, Vol 11, Issue 1, p1
- ISSN
2045-3701
- Publication type
Article
- DOI
10.1186/s13578-021-00564-x