Dietary polyphenols mitigate SARS-CoV-2 main protease (Mpro)–Molecular dynamics, molecular mechanics, and density functional theory investigations

Potential inhibitory properties of structurally modified quercetin/isohamnetin glucosides against SARS-CoV-2 Mpro; molecular docking and dynamics simulation strategies

“…Hence, the complexes of Mpro-ISM-1, Mpro-QM-2, and Mpro-QD-6 are more compact. These values are lower than the minimum values recorded for dexamethasone reported elsewhere [ 32 ]. Interestingly, the quercetin and isoharmetin exhibited more compactness when bound to SARS-CoV-2-Mpro when compared to already established inhibitors [ 18 ].…”

“…Mpro-ISD-3 with the highest average number of HB tends to be most stable in tandem with ellagic acid, which had an average HB of 1.81. Due to obvious reasons, these compounds might be highly stable than remdesivir and kievitone a polyphenolic compound which had average intermolecular hydrogen bonds of 1.50 and 1.04 respectively [ 32 ]. Other antioxidant compounds have been demonstrated to bind the SARS-CoV-2-Mpro via hydrogen bonds thus enhancing the binding stability [ 8 ].…”

“…The contributing MM-PBSA energies (kJ/mol) obtained were Lys 5 (3.97, 0.8914, 2.5112, 1.8592, 3.5971), Arg 131 (0.3553, 1.505, −2.1189, 0.4727, 0.0077), Lys 137 (−0.743, 0.7518, 4.5830, 0.9065,1.6301), Asp 197 (−0.1731,-1.2884, 0.8357, 0.0944,-1.7021), Thr 198 (−0.0015, −0.6805, −2.8456, −0.2493, −0.2124), Thr 199 (−0.0078, −4.5339, −5.432, −0.2286, 0.1801), Leu 272 (−0.0025, −8.710, −5.2098, −5.6753, −0.0130), Leu 287 (−0.0095, −8.3774, −3.5868, 0.0782, 1.1932), Glu 288 (−1.1861, −2.0213, −1.8222, −2.7281,-0.5178), Asp 289 (−0.6581, −1.4791, −2.4043, 0.0782, 1.1712), and Glu 290 (0.0465, −0.9335, −0.9158, 0.0038, 1.4138) for Mpro-ISM-1, Mpro-ISD-3, Mpro-IST-2, Mpro-QM-2, and Mpro-QD-6 respectively. Residues His 41 and Cys 145 of the catalytic triad of the SARS-CoV-2-Mpro had contributing MM-PBSA energies of His 41 (−0.0378, 0.0068, −0.0031, −0.0107,-0.07401) and Cys 145 (−0.0384, 0.0007, −0.0008, −0.0046, −0.0231) for Mpro-ISM-1, Mpro-ISD-3, Mpro-IST-2, Mpro-QM-2, and Mpro-QD-6 respectively [ 32 ]. reported somewhat higher decomposition energies for ellagic acid, kievitone, and remdesivir, therefore our observation in this study reflects strong interaction between the ligands and SARS-CoV-2-Mpro.…”

“…It cleaves the viral polyprotein together with the papain-like protease to form 16 non-structural proteins [ 22 , 28 ] that are involved in viral replication, transcriptional processes and is thus essential for the viral life cycle [ 22 , 29 , 30 ]. Because of the unique function of the Mpro in the survival and viability of the SAR-CoV-2, it has attracted a great deal of scientific attention as an important target to block viral propagation [ 18 , 26 , [31] , [32] , [33] ]. Notably, from our study, the inhibitory activity of the quercetin glucoside and isorhamnetin glucoside increased as the number of glucoside residues increased [ 26 ].…”

In silico evaluation of Vitis amurensis Rupr. Polyphenol compounds for their inhibition potency against COVID-19 main enzymes Mpro and RdRp

“…Compound 2 exhibits both anti-hepatitis B virus (HBV) and anti-hepatitis C virus (HCV) functions ( Wohlfarth and Efferth 2009 ). A molecular docking analysis of 2 against the SARS-CoV-2 M pro enzyme (PDB ID: 6LU7) showed that it interacts through hydrogen and hydrophobic bonds with the amino acid residues His41, Met49, Asn142, Gly143, Cys145and Glu166 with a binding energy of -8.9 Kcal/mol ( Adelusi et al 2022 ) ( Table 2 ). Compound 2 interacts with the RdRp residues Thr246, Arg249, Ser255 and Pro461 with a docking energy of -7.6 Kcal/mol ( Gowrishankar et al 2021 ) ( Table 3 ).…”