Molecular Mechanism of Inhibition of SARS-COV-2 Binding to Host Receptor by Antiviral Flavonoids; Bavachinin, Corylifoln and Luteolin

The worldwide SARS-COV-2 outbreak caused COVID-19 pandemic. Understanding the mechanism of host receptor recognition by virus is inevitably helpful for developing appropriate drugs and treatment strategies.

In the present study, applying a standard systematic review protocol, we surveyed the literature using Google Scholar and PubMed for experimental reports on the plant derived compounds effective against coronavirus family members. Original articles meeting the inclusion criteria for the present study were selected and underwent more scrutiny for introducing plant compounds for further analysis. The interaction of the compounds with receptor binding domain (RBD) of SARS-COV-2 spike protein was analyzed using molecular docking analysis. Top three compounds with the best binding affinity to RBD were selected and their mechanisms of interaction were investigated using Pymol, MOE, and Ligplot softwares.

Three herbal compounds, bavachinin, croylifol, and luteolin with ΔG values of -8.4, -8.1, and -7.6, respectively, showed the best interaction with RBD and inhibition of virus-host binding among 24 compounds analyzed. The binding of these ligands to RBD was mediated through receptor binding motif (RBM) and a group of amino acids including Leu455, Gln493, and Asn501.

Considering the experimental antiviral effects as well as favorable interaction with SARS-COV-2 spike protein, bavachinin, croylifol, and luteolin are suggested for use in clinical trial investigations of COVID-19