6VH3
2.20 A resolution structure of MERS 3CL protease in complex with inhibitor 7j
Summary for 6VH3
| Entry DOI | 10.2210/pdb6vh3/pdb |
| Descriptor | Orf1a protein, (1S,2S)-2-[(N-{[(4,4-difluorocyclohexyl)methoxy]carbonyl}-L-leucyl)amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid (3 entities in total) |
| Functional Keywords | protease, mers 3cl protease inhhibitors, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Middle East respiratory syndrome-related coronavirus |
| Total number of polymer chains | 2 |
| Total formula weight | 69683.64 |
| Authors | Lovell, S.,Battaile, K.P.,Kashipathy, M.M.,Rathnayake, A.D.,Zheng, J.,Kim, Y.,Nguyen, H.N.,Chang, K.O.,Groutas, W.C. (deposition date: 2020-01-09, release date: 2020-08-12, Last modification date: 2024-11-20) |
| Primary citation | Rathnayake, A.D.,Zheng, J.,Kim, Y.,Perera, K.D.,Mackin, S.,Meyerholz, D.K.,Kashipathy, M.M.,Battaile, K.P.,Lovell, S.,Perlman, S.,Groutas, W.C.,Chang, K.O. 3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice. Sci Transl Med, 12:-, 2020 Cited by PubMed Abstract: Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses. PubMed: 32747425DOI: 10.1126/scitranslmed.abc5332 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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