Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication.

Publication date: Sep 15, 2023

Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple structure-activity relationships were identified among active compounds such as enrichment of galloylated flavonoids and biflavones, including multiple biflavone analogs of apigenin. In a cell-based SARS-CoV-2 replication assay, the most potent inhibitors were apigenin and the galloylated pinocembrin analog, pinocembrin 7-O-(3”-galloyl-4”,6”-(S)-hexahydroxydiphenoyl)-beta-D-glucose (PGHG). Molecular dynamic simulations predicted that PGHG occludes the S1 binding site via a galloyl group and induces a conformational change in Mpro. These studies will advance the development of plant-based flavonoids-including widely available natural products-to target β-coronaviruses.

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Concepts Keywords
Coronaviruses Biochemistry
Flavonoids Biological sciences
Hexahydroxydiphenoyl Cell biology
Therapy Chemistry
Natural product chemistry
Natural sciences


Type Source Name
pathway KEGG Viral replication
disease IDO replication
disease MESH COVID-19
drug DRUGBANK Apigenin
disease IDO cell
disease IDO assay
drug DRUGBANK Beta-D-Glucose
disease IDO site
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Chymotrypsin
drug DRUGBANK L-Cysteine
disease VO effective
drug DRUGBANK Ritonavir
disease IDO host
pathway REACTOME Metabolism
disease MESH Thrombosis
disease VO USA
disease MESH Emerging Infectious Diseases
drug DRUGBANK Dimethyl sulfoxide
disease VO URE
disease VO dose
drug DRUGBANK Coenzyme M
disease IDO production
drug DRUGBANK Flavone

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