Table 2.
Amino acid residues and type of interaction involved in binding of standard ligands and W. somnifera lead phytochemicals with target SARS-CoV-2 and human host proteins
| S. No. | Compound name | Hydrogen binding site | Hydrophobic binding site |
|---|---|---|---|
| SARS-CoV-2 Spike Glycoprotein | |||
| 1 | VE607 | Gln493(3.00), Ser494(2.96; 3.21), Tyr495(3.06) | Asn422, Asp442, Leu492, Pro491, Phe497, Tyr351, Tyr421, Val350 |
| 2 | Galactitol | Gln493(2.95; 2.72; 3.05), Ser494(2.96), Tyr495(3.19), Val350(3.03) | Asn422, Leu492, Ser349 |
| 3 | Chlorogenic acid | Asn422(2.95), Gln493(2.90; 2.85, 2.97), Phe347(2.93; 3.01) | Ala348, Ile418, Lys417, Leu492, Phe497, Ser349, Ser494, Tyr351, Tyr495, Val350, Val401 |
| 4 | Quercetin-3-rutinoside-7-glucoside | Pro491(2.95), Ser494(2.78, 2.71), Tyr495(3.05) | Asn422, Gln493, Ile418, Lys417, Leu492, Ser349, Tyr351 |
| 5 | Isochlorogenic acid B | Asp422(2.73, 3.07), Gln493(2.80), Phe347(3.31), Tyr351(3.11) | Lys417, Phe497, Ser349, Ser494, Tyr495, Val350, Val401 |
| 6 | Rutin | Asp442(2.59), Arg509(3.27), Phe347(2.95, 2.68), Phe497(2.71), Ser494(2.93), Thr345(2.76, 2.81), Tyr495(3.09) | Arg346 |
| 7 | Quercetin | Asp442(2.74, 2.76), Val350(2.86) | Phe497, Ser349, Tyr495, Val401 |
| 8 | Caffeoyl-quinic acid | Gln493(2.94), Ser494(2.96), Tyr351 (2.34), Tyr495(3.08) | Asn422, Ser349, Val350 |
| Human CD26 | |||
| 1 | Sitagliptin | Arg669(3.05), Asp708, Glu206, His740, Ser630 | Arg125, Arg358, Asn710, Glu205, Phe357, Ser209, Tyr547, Tyr662, Tyr666, Val207 |
| 2 | Quercetin-3-rutinoside-7-glucoside | Arg358(2.72, 2.85), Asp302(2.64, 2.82, 3.08), Glu205(2.96), Glu206(2.74), Glu361(2.73), Ile405(2.94, 3.17), Tyr662(3.07), Val207(3.18) | Arg125, Arg356, Phe208, Phe357, Ser209, Trp215, Tyr585, Tyr666 |
| 3 | Rutin | Arg125(2.89, 3.33), Glu206(2.94, 3.03), Ser209(2.96), Ser630(3.20, 2.97), Tyr547(2.63), Tyr662(2.73, 2.83) | Glu205, Gln553, Lys554, Phe357, Ser552, Trp629, Tyr666, Val207 |
| 4 | Caffeoyl quinic acid | Arg125(3.26, 2.93), Asn710(3.03), Cys551(2.78), Glu206(2.85), Gln553(3.04), Tyr547(2.77) Tyr585(3.08) Tyr662(2.80) | His740, Glu205, Phe357, Ser552, Tyr666, Ser630 |
| 5 | Sitoindosite X | Arg356(2.94), Gln553(3.20), Lys554(3.0) | Arg125, Asp739, Glu361, Gly741, His740, Ile405, Phe357, Ser360, Tyr546, Tyr547, Tyr585, Trp629 |
| 6 | Dulcitol | Arg358(3.16), Arg669(3.08), Glu205(3.06), Glu206(2.85), Ser209(2.84, 3.01, 3.19), Val207(2.78) | Tyr666, Phe357 |
| Human TMPRSS2 | |||
| 1 | Camostat mesylate | Arg277(2.99), Tyr227(3.00) | Phe394, Ile279, Thr324, Pro325, Phe231, Ala280, phe193, Cys278, Gly190, Leu188 |
| 2 | Rutin | Arg219(2.76, 3.79), Asn229(2.29), Glu326(2.87, 2.81), Trp327(3.01) | Arg526, Ile279, Lys228, Phe231, Pro391, Tyr232, Thr324 |
| 3 | Isochlorogenic acid B | Asn229(2.76), Asp528(2.67), Met525(2.98), Lys387(3.03), Cys278(3.24) | Ala280, Lys228, Trp327, Arg277, Phe231, Ile279, Pro325, Thr324, Glu326 |
| 4 | Caffeoyl-quinic acid | Arg277(2.73), Asn229(3.05), Glu326(2.86) | Ala280, Cys278, Ile279, Met525, Phe231, Phe394, Thr324, Trp327 |
| 5 | 4-2-3-Didehydrosomnifericin | Asn229(3.30), Glu326(2.62), Leu392(3.24), Trp327(3.24) | Ile279, Met525, Phe231, Pro325, Pro391, Thr324, Thr393, |
| 6 | Chlorogenic acid | Asn229(2.97), Met525(3.08) | Asp528, Glu326, Ile279, Lys228, Phe231, Pro325, Thr324 |
| SARS-CoV-2 RdRp | |||
| 1 | Remdesivir | Arg553(3.08, 2.83), Thr556(3.25), Asp623(2.39), Cys622(2.85), Tyr619(2.77) | Asp452, Arg24, Arg555, Tyr455, Ala554, Lys621, Asp618, Asp760 |
| 2 | Quercetin-3-rutinoside-7-glucoside | Asp618(2.73), Asp623(2.88, 2.98), Asp760(2.88), Asp761(3.22), Glu811(2.96), Lys621(2.75), Lys798 (2.36), Ser814(3.31), Trp800(3.00) | Arg553, Pro620, Trp617, Tyr619 |
| 3 | Rutin | Asp760(2.85, 2.83), Lys551(3.33), Lys621(2.84, 2.85), Lys798(2.89), Tyr619(2.74, 3.29), Trp800(2.90) | Arg553, Asp618, Asp761, Cys662, Gly616, Ser814, Ser759, Trp617, |
| 4 | Chlorogenic acid | Asp618(3.21), Lys551(2.91), Lys621(2.81), Lys798(2.92), Tyr619(3.18), Trp800(3.09) | Asp760, Asp761, Glu811, Pro620, Trp617 |
Numerical values given in bracket represent hydrogen bond length in Å
Analysis of phytochemical groups and binding efficacy against targeted proteins showed that flavonoid/polyphenolics showed lowest binding followed by other groups, saponins, alkaloids and steroidal/benzenoid lactone (Fig. 6).The binding free energies of SARS-CoV-2 spike glycoprotein- Galactitol, RdRP- Quercetin-3-rutinoside-7-glucoside, TMPRSS2-rutin and CD26- Quercetin-3-rutinoside-7-glucoside were calculated by using MM-GBSA method and the results are shown in Fig. 7. Mostly the overall binding free energy of all the protein ligand complexes was more negative in comparison to unbound protein