Dataset Information

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 | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Xiong Yuan Y Zhu Guang-Hao GH Wang Hao-Nan HN Hu Qing Q Chen Li-Li LL Guan Xiao-Qing XQ Li Hui-Liang HL Chen Hong-Zhuan HZ Tang Hui H Ge Guang-Bo GB

Fitoterapia 20210422

3-Chymotrypsin-like protease (3CLpro) 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 3CLpro inhibitors from herbal constituents, as well as to investigate the inhibitory mechanism of the newly identified efficacious SARS-CoV-2 3CLpro inhibitors. Following screening of the inhibitory potentials of eighty herbal products against S ...[more]

PMID: 33894315

Similar Datasets

Project description:BackgroundThe 3C-like proteases (3CLpros) are cysteine-rich homodimeric proteins and can be covalently modified by numerous natural and synthetic compounds, which in turn, block the proteolytic activity or the formation of enzymatically active dimeric forms. Although herbal medicines have been widely used to treat COVID-19, identification of the key herbal constituents that can covalently modify the 3CLpros in β-coronaviruses (CoVs) remains a big challenge.AimsTo construct a comprehensive approach for efficient discovering the covalent SARS-CoV-2 3CLpro inhibitors from herbal medicines. To decipher the key anti-SARS-CoV-2 3CLpro constituents in Ginkgo biloba extract 50 (GBE50) and to study their anti-SARS-CoV-2 3CLpro mechanisms.MethodsSARS-CoV-2 3CLpro inhibition assay including time-dependent inhibition assays and inactivation kinetic analyses were conducted using a fluorescence-based biochemical assay. The constituents in GBE50 were analyzed by UHPLC-Q-Exactive Orbitrap HRMS. The peptides modified by herbal constituents were characterized by using nanoLC-MS/MS.ResultsFollowing testing the anti-SARS-CoV-2 3CLpro effects of 104 herbal medicines, it was found that Ginkgo biloba extract 50 (GBE50) potently inhibited SARS-CoV-2 3CLpro in dose- and time-dependent manners. A total of 38 constituents were identified from GBE50 by UHPLC-Q-Exactive Orbitrap HRMS, while 26 peptides modified by 18 constituents were identified by chemoproteomic profiling. The anti-SARS-CoV-2 3CLpro effects of 18 identified covalent inhibitors were then validated by performing time-dependent inhibition assays. The results clearly demonstrated that most tested constituents showed time-dependent inhibition on SARS-CoV-2 3CLpro, while gallocatechin and sciadopitysin displayed the most potent anti-SARS-CoV-2 3CLpro effects.ConclusionCollectively, GBE50 and some constituents in this herbal product could strongly inhibit SARS-CoV-2 3CLpro in dose- and time-dependent manner. Gallocatechin and sciadopitysin were identified as potent SARS-CoV-2 3CLpro inhibitors, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets