6XQS
Room-temperature X-ray Crystal structure of SARS-CoV-2 main protease in complex with Telaprevir
Summary for 6XQS
| Entry DOI | 10.2210/pdb6xqs/pdb |
| Descriptor | 3C-like proteinase, (1S,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino]acetyl}amino)-3,3-dimethylbutanoyl]-N-[(2R,3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl]octahydrocyclopenta[c]pyrrole-1-carboxamide (3 entities in total) |
| Functional Keywords | 3c like proteinase, viral protein, viral protein-hydrolase complex, viral protein/hydrolase |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 1 |
| Total formula weight | 34507.41 |
| Authors | Kneller, D.W.,Kovalevsky, A.,Coates, L. (deposition date: 2020-07-10, release date: 2020-07-22, Last modification date: 2024-11-13) |
| Primary citation | Kneller, D.W.,Galanie, S.,Phillips, G.,O'Neill, H.M.,Coates, L.,Kovalevsky, A. Malleability of the SARS-CoV-2 3CL M pro Active-Site Cavity Facilitates Binding of Clinical Antivirals. Structure, 28:1313-, 2020 Cited by PubMed Abstract: The COVID-19 pandemic caused by SARS-CoV-2 requires rapid development of specific therapeutics and vaccines. The main protease of SARS-CoV-2, 3CL M, is an established drug target for the design of inhibitors to stop the virus replication. Repurposing existing clinical drugs can offer a faster route to treatments. Here, we report on the binding mode and inhibition properties of several inhibitors using room temperature X-ray crystallography and in vitro enzyme kinetics. The enzyme active-site cavity reveals a high degree of malleability, allowing aldehyde leupeptin and hepatitis C clinical protease inhibitors (telaprevir, narlaprevir, and boceprevir) to bind and inhibit SARS-CoV-2 3CL M. Narlaprevir, boceprevir, and telaprevir are low-micromolar inhibitors, whereas the binding affinity of leupeptin is substantially weaker. Repurposing hepatitis C clinical drugs as COVID-19 treatments may be a useful option to pursue. The observed malleability of the enzyme active-site cavity should be considered for the successful design of specific protease inhibitors. PubMed: 33152262DOI: 10.1016/j.str.2020.10.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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