Hat of reference inhibitors. The compounds glycycoumarin, Inophyllum P, oxypeucedanin hydrate, and mesuol have been located to exhibit the ideal docking scores of – 11.89, – 11.43, – 11.76, and – 11.17 kcal/mol, respectively, among the coumarin phytochemicals against 3CLpro of SARS-CoV-2, even though glycycoumarin had the highest binding affinity to that of SARSCoV and MERS-CoV (Table 1). Therefore, glycycoumarin was the best docked compound to 3CLpro that interacted strongly together with the target protein on the coronavirus. Analysis of the interactions from the very best coumarin phytochemicals and reference inhibitors with amino acid residues of 3CLpro of coronaviruses (Table 1) showed that these compounds majorly interacted with the hotspot residues via hydrophobic interactions and with H-bonding under four.0 (particularly with Cys145 and His41). The outcomes of your molecular docking of your best coumarin phytochemicals including glycycoumarin, Inophyllum P, mesuol, oxypeucedanin hydrate and reference inhibitors in the active site of SARS-CoV-2 3CLpro illustrated by their corresponding 2D interaction plots that the chosen compounds interacted with either each (Cys145 and His41) or at the least 1 catalytic dyad residue, detected by MOE (Fig. 3 and Fig. S5) [1, 18, 32, 43, 51]. The selected compounds and Ritonavir and lopinavir exhibit equivalent binding modes due to the parallel orientations from the ligands and their identical crucial residues (Fig. 3), like His41, Met49, Phe140, Leu141, Asn142, Gly143, Ser144, Cys145, Met165, His164, Glu166, Gln189, and Thr190. The results of ligand rotein binding interaction showed that ritonavir and lopinavir as reference inhibitors have been docked into the active web-site and catalytic dyad (Cys145 and His41) of SARS-CoV-2. Ritonavir could kind two hydrogen bonds using the side chain of Thr25 plus the backbone of Glu166 (Fig. 3a), whilst lopinavir using a considerably greater binding energy (- 10.890 kcal/mol) than Ritonavir showed significant – stacking interaction with His41 on the catalytic dyad and type one particular hydrogen bond using the side chain of Gln189 (Table 1, Fig. 3b) as well as, each on the inhibitors had hydrophobic interactions with surrendering residues. Glycycoumarin, a reported anti-viralScores (kcal/mol)Molecular Diversity (2022) 26:1053076 Table 1 Interacting amino acid (aa) residues of 3CLpro of coronaviruses together with the best coumarin phytochemicals Bioactive compound Ritonavir Coronavirus Interacted residuesaa residue involved in H-bonding (Bond Distance) Glu166 (2.48), Thr25 (three.72) Gln189 (two.08) Cys145 (two.46), Ser144 (1.91), Gln189 (2.15) Cys145 (2.607), Ser144 (two.23), Leu141 (three.18) Cys145 (2.608), Ser144 (three.77), Neurotensin Receptor MedChemExpress Asn142 (1.27) Cys145 (three.04), Ser144 (two.21), His163 (two.86), His164 (3.04) His164 (two.41), Cys44 (two.51), Thr24 (two.30) His164 (two.862), Glu166 (3.09), Asn142 (2.47) His163 (2.35), Thr25 (two.29, thr45 (3.72) Glu166 (2.07), Ser144 (1.72), Leu141 (2.02) Met6 (two.21), Asp295 (two.16), Caspase Accession Asn156 (1.93) Gln299 (1.790), Asn156 (3.58), Gly157 (three.21) Glu155 (2.56), ser116 (2.48), Thr130 (three.22), Asp295 (2.84) Gln299 (3.14), Ser114 (three.09)SARS-CoV-2 His 41, Cys145, Gly143, Met165, His164, Glu166, Asn142, Met49, Gln189, Thr26, Thr24, Thr25, Thr45, Ser46 Lopinavir His 41, Cys145, Gly143, Met165, His164, Glu166, Asn142, Leu141, Phe140, Met49, Gln189, Asp187 Glycycoumarin His 41, Cys145, Ser144, Gly143, Met165, His164, Glu166, Asn142, Leu141, Phe140, Met49, Gln189, Asp187, Arg188, Tyr54 Inophyllum P His 41, Cys145, Ser144, Gly143, Met165, His164, Glu166, A.