Identification of antiviral phytochemicals from cranberry as potential inhibitors of SARS-CoV-2 main protease (Mpro)

Cranberry phytochemicals are known to possess antiviral activities. In the current study, we explored the therapeutic potential of cranberry against SARS-CoV-2 by targeting its main protease (Mpro) enzyme. Firstly, phytochemicals of cranberry origin were identified from three independent databases. Subsequently, virtual screening, using molecular docking and molecular dynamics simulation approaches, led to the identification of three lead phytochemicals namely, cyanidin 3-O-galactoside, β-carotene and epicatechin. Furthermore, in vitro enzymatic assays revealed that cyanidin 3-O-galactoside had the highest inhibitory potential with IC50 of 9.98 μM compared to the other two phytochemicals. Cyanidin 3-O-galactoside belongs to the class of anthocyanins. Anthocyanins extracted from frozen cranberry also exhibited the highest inhibitory potential with IC50 of 23.58 μg/ml compared to the extracts of carotenoids and flavanols, the class for β-carotene and epicatechin, respectively. Finally, we confirm the presence of the phytochemicals in the cranberry extracts using targeted LC-MS/MS analysis. Our results, therefore, indicate that the identified cranberry-derived bioactive compounds as well as cranberry could be used for therapeutic interventions against SARS-CoV-2. •Main protease (Mpro) is involved in viral replication of SARS-CoV-2•Virtual screening identified 3 cranberry phytochemicals with strong binding affinity for Mpro•These bioactive compounds were cyanidin 3-O-galactoside, β-carotene and epicatechin•Chemical standards of the phytochemicals showed micromolar IC50 values in enzymatic assay•Anthocyanins extracted from cranberry showed highest inhibition of Mpro