Table 1.
Molecular docking analysis of eight antiviral compounds (parecoxib, chlortetracycline, ivermectin B1a, ivermectin B1b, sulfasalazine, remdesivir, atovaquone, and nirmatrelvir) against their respective SARS-CoV-2 target proteins (nsp3, nsp5, nsp12, and spike). The 3D structure of four target proteins of the reference strain and the two variants Delta and Omicron were modeled before docking with inhibitors. The hydrogen bond-forming residues from the pool of interacting residues of each target protein are highlighted in bold. While we display all interacting residues from the reference strain, the interacting residues that were different from the reference are displayed for two variants for better readability. Refer to Figure S1 for visualization of inhibitors and target interactions.
| Protein | Drug | Variant | Binding Affinity (kcal/mol) | Residues Involved in Interactions |
|---|---|---|---|---|
| nsp3 | Parecoxib | Reference | −8.4 | Ala242, Gly250, Gly251, Gly252, Val253, Ala333, Gly334, Ile335, Phe336, Ala358, Phe360, Leu364, Val539 |
| Delta | −8.4 | Val359 | ||
| Omicron | −8.2 | Asp226, Ile227, Ala256, Pro329, Leu330, Val359, Asp361 | ||
| Chlortetracycline | Reference | −8.5 | Asp226, Ile227, Val228, Val253, Ala256, Pro329, Leu330, Ala333, Gly334, Val359, Phe360, Asp361, Leu364 | |
| Delta | −8.5 | No unique residues identified | ||
| Omicron | −8.5 | No unique residues identified | ||
| nsp5 | Nirmatrelvir | Reference | −7.7 | Phe140, Leu141, Asn142, Cys145, His163, Met165, Glu166, His172, Arg188, Gln189, Thr190, Gln192 |
| Delta | −7.6 | His41, Met49, Leu167, Pro168, Asp187 | ||
| Omicron | −7.8 | His41, Met49, Asp187 | ||
| Ivermectin B1b | Reference | −10.2 | Thr26, His41, Ser46, Met49, Asn119, Gly143, Cys145, Met165, Glu166, Pro168, Arg188, Gln189, Thr190, Gln192 | |
| Delta | −9.8 | Thr24, Thr25, Asn142, Ala191 | ||
| Omicron | −10.2 | No unique residues identified | ||
| nsp12 | Sulfasalazine | Reference | −9.6 | Arg583, Gly584, Gly597, Ser592, His599, Asn600, Met601, Lys603, Thr604 |
| Delta | −9.6 | No unique residues identified | ||
| Omicron | −9.3 | No unique residues identified | ||
| Remdesivir | Reference | −6.4 | Arg553, Asp618, Tyr619, Pro620, Lys621, Cys622, Asp623, Asn691, Ser759, Asp760, Asp761, Glu811, Ser814 | |
| Delta | −7.4 | Tyr455, Arg624, Ser682, Thr687 | ||
| Omicron | −8 | Tyr455, Arg533, Lys545, Arg555, Thr556, Trp617, Arg624, Ser682 | ||
| Spike | Ivermectin B1a | Reference | −10 | Lys811, Pro812, Ser813, Arg815, Asp820, Phe823, Gly832, Phe833, Ile834, Lys854, Val860, Thr866, Glu868 |
| Delta | −10 | No unique residues identified | ||
| Omicron | −10 | No unique residues identified | ||
| Atovaquone | Reference | −7.3 | Thr732, Leu828, Ala831, Gly832, Phe833, Ile834, Val860, Pro862 | |
| Delta | −7.3 | No unique residues identified | ||
| Omicron | −7.3 | No unique residues identified |