Phytochemicals of Rhus spp. as Potential Inhibitors of the SARS-CoV-2 Main Protease: Molecular Docking and Drug-Likeness Study

Background. The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. Aim. In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (M-pro; 6LU7). Methods. 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SA RS-CoV-2 M-pro. Results. The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 M-pro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyI)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of M-pro that may be used for the treatment of COVID-19. Conclusion. Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against M-pro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SA RS-CoV-2.

Automated summary

The study found that 26 active polyphenolic compounds in sumac showed potential inhibitory effects against the SARS-CoV-2 main protease enzyme. Among them, six active polyphenolic compounds were identified as potential inhibitors of M-pro for the treatment of COVID-19, showing promising results in molecular docking, drug likeness, and synthetic accessibility score analysis.