Computational Investigation of Bioactive Phytoconstituents as SarS-Cov-2 Main Protease Inhibitors Through Molecular Docking and Interaction Fingerprint Studies

Since 2019, the SARS-CoV-2 infection has continued to cause significant human suffering. Numerous investigations into the viral pathogenesis have led to converging conclusions on how the virus enters and spreads within the host. The main protease (Mpro) of coronaviruses has been considered as an attractive therapeutic target because of its important role in processing polyproteins translated from viral RNA. Many studies discovered that phytoconstituents possess potent antiviral activities. Hence, in the present work, 439 co-crystal ligands of SARS-CoV-2 Mpro were collected and docked with Mpro of SARS-CoV-2 (PDB ID:7AEH) to identify best crystal ligand. Among all the crystal ligands collected, HF0 (7-O-methyl-dihydromyricetin) showed good XP G score -7.872 Kcal/Mol and it was selected as reference to compare the docking scores of phytoconstituents. Then, molecular docking study was performed for 274 antiviral phytoconstituents from various medicinal plants against Mpro of SARS-CoV-2. Molecular docking studies found that seven phytoconstituents exhibited better docking scores than best co-crystal ligand HF0. Among the seven best docked phytoconstituents, 3,4-dicaffeoylquinic acid showed good interactions with key amino acid residues in substrate binding site of Mpro with XPG Score –9.721 Kcal/Mol. Qikprop results indicated that the most phytoconstituents have demonstrated favourable pharmacological characteristics. Interaction fingerprint analysis revealed that all the seven best docked phytoconstituents of the present study bound to Glu166, key residue situated in the centre of the substrate binding site of Mpro resulting in the reduction of the catalytic activity of main protease thus blocking the replication of SARS-CoV-2.