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Ginkgolic acid and anacardic acid are specific covalent inhibitors of SARS-CoV-2 cysteine proteases.

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 (PL^pro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CL^pro) in addition to PL^pro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CL^pro and PL^pro. 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.

SUBMITTER: Chen Z

PROVIDER: S-EPMC7914117 | biostudies-literature |

REPOSITORIES: biostudies-literature

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