Table 1.
Binding of covalent and non-covalent SARS-CoV PLpro inhibitors to SARS-CoV-2 PLpro, OTUB1, and OTUB2. Analysis of relevant hydrogen bonding and hydrophobic protein-ligand interactions.
| Compound | Target Protein | Hydrogen Bond Interactions | Hydrophobic Interactions * |
|---|---|---|---|
| 1 | SARS-CoV-2 PLpro | - | - |
| OTUB1 | Pro1263 | His1265 | |
| OTUB2 | Thr222, Asn226 | His224 | |
| 2 | SARS-CoV2 PLpro | Ala288 | - |
| OTUB1 | Glu1060, Pro1263 | - | |
| OTUB2 | Lys221, Thr222, Asn226 | His224 | |
| 3 | SARS-CoV2 PLpro | Cys111 | |
| OTUB1 | - | - | |
| OTUB2 | - | - | |
| 4 | SARS-CoV2 PLpro | Cys111, Gly163, Tyr268 | Tyr264, His272 |
| OTUB1 | Pro1087, Asp1216 | Tyr1261 | |
| OTUB2 | Thr45, Gly47 | His224 | |
| 5 | SARS-CoV2 PLpro | Cys111, Tyr112, Tyr264 | Tyr264, His272 |
| OTUB1 | Gly1264 | - | |
| OTUB2 | Arg49, Ser223 | - | |
| 6 | SARS-CoV2 PLpro | - | His272, Trp106 |
| OTUB1 | Glu1060 | - | |
| OTUB2 | Thr45 | - |
* Mostly π-π interactions. Active site residues are given in bold.