Indian red rice phenolic metabolites as potential natural inhibitors of SARS-CoV-2 main protease: A metabolomic and in silico study

Abstract

COVID-19 is a viral respiratory infectious disease caused by the novel strain of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). SARS-CoV-2 main protease (M-pro) is associated with viral replication and transcription, thereby making it a potent target for combating COVID-19. Natural compounds from plants are being widely explored for viral inhibitors due to their safety aspect. Therefore, the present study aimed at predicting the antiviral property of red rice phenolic metabolites (RRPM) from three Indian rice varieties against SARS-CoV-2 M-pro through metabolomics and in silico studies. The Indian red rice cultivars, i.e., Veethi vadankan, Samba mosanam and Kuzhiadichan, were subjected to Q-TOF-LC-MS analysis and eighteen abundant polyphenols were selected using hierarchical cluster analysis. The abundant RRPM were virtually screened using Swiss ADME, a web-based tool. All the abundant polyphenols obeyed the Lipinski's rule except for hesperetin 3'-O-glucuronide, thereby exhibiting drug likeliness. Based on ADME analysis, fifteen of the RRPM showed good oral bioavailability, high GI absorption and acceptable overall bioavailability score. The 15 RRPM were further subjected to molecular docking analysis using Auto dock 1.5.6 against SARS-CoV-2M(pro). The analysis revealed 7, 4'-dihydroxy flavone and eriodictyol to have strong binding affinity (>10 kcal/mol) higher than nelfinavir (-8.53 kcal/mol). Eight other compounds also proved to be potential natural inhibitors of SARS-CoV-2 M-pro. The present study has revealed Kuzhiadichan as a good source of eight potent natural inhibitors of SARS-CoV-2 M-pro and as a potential functional food for COVID-19 management.