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 (IC 50 = 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 (IC 50 < 10 μM). Among all tested constituents, GA C15:0, GA C17:1 and sciadopitysin displayed potent 3CL pro inhibition activities, with IC 50 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 pro via 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 .
Keywords: Bioflavones; Ginkgo biloba leaves; Ginkgolic acids; Inhibitory mechanism; SARS-CoV-2 3CL(pro).
【저자키워드】 Bioflavones, Ginkgo biloba leaves, Ginkgolic acids, Inhibitory mechanism, SARS-CoV-2 3CL(pro)., 【초록키워드】 SARS-CoV-2, Coronaviruses, 3CL pro, docking, protease, inhibition, inhibitors, Viral, viral replication, medication, inhibitor, mechanism, broad spectrum, Chymotrypsin-like protease, kinetic, Ginkgo biloba, Compound, activities, Ginkgo, Inhibition assays, proteinase, offer, inhibitory, inhibition activity, tested, less, demonstrated, inhibit SARS-CoV-2, 【제목키워드】 SARS-CoV-2, inhibitor,