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Discovery of naturally occurring inhibitors against SARS-CoV-2 3CL^pro from Ginkgo biloba leaves via large-scale screening.

ABSTRACT: 3-Chymotrypsin-like protease (3CL^pro) is a virally encoded main proteinase that is pivotal for the viral replication across a broad spectrum of coronaviruses. This study aims to discover the naturally occurring SARS-CoV-2 3CL^pro inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CL^pro inhibitors. Following screening of the inhibitory potentials of eighty herbal products against SARS-CoV-2 3CL^pro, Ginkgo biloba leaves extract (GBLE) was found with the most potent SARS-CoV-2 3CL^pro inhibition activity (IC₅₀ = 6.68 μg/mL). Inhibition assays demonstrated that the ginkgolic acids (GAs) and the bioflavones isolated from GBLE displayed relatively strong SARS-CoV-2 3CL^pro inhibition activities (IC₅₀ < 10 μM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CL^pro inhibition activities, with IC₅₀ values of less than 2 μM. Further inhibition kinetic studies and docking simulations clearly demonstrated that two GAs and sciadopitysin strongly inhibit SARS-CoV-2 3CL^provia a reversible and mixed inhibition manner. Collectively, this study found that both GBLE and the major constituents in this herbal product exhibit strong SARS-CoV-2 3CL^pro inhibition activities, which offer several promising leading compounds for developing novel anti-COVID-19 medications via targeting on 3CL^pro.

SUBMITTER: Xiong Y

PROVIDER: S-EPMC8061081 | biostudies-literature |

REPOSITORIES: biostudies-literature

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