8W1U
SARS-CoV-2 Main protease bound to non-covalent lead molecule NZ-804
This is a non-PDB format compatible entry.
Summary for 8W1U
| Entry DOI | 10.2210/pdb8w1u/pdb |
| Related | 8W1T |
| Descriptor | 3C-like proteinase nsp5, 11-[1-(1H-pyrrolo[3,2-c]pyridine-7-carbonyl)piperidin-4-ylidene]-6,11-dihydro-5H-5lambda~6~-dibenzo[b,e]thiepine-5,5-dione, DIMETHYL SULFOXIDE, ... (4 entities in total) |
| Functional Keywords | protease, inhibitor, complex, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV, COVID-19 virus) |
| Total number of polymer chains | 2 |
| Total formula weight | 68746.47 |
| Authors | |
| Primary citation | Zhou, N.E.,Tang, S.,Bian, X.,Parai, M.K.,Krieger, I.V.,Flores, A.,Jaiswal, P.K.,Bam, R.,Wood, J.L.,Shi, Z.,Stevens, L.J.,Scobey, T.,Diefenbacher, M.V.,Moreira, F.R.,Baric, T.J.,Acharya, A.,Shin, J.,Rathi, M.M.,Wolff, K.C.,Riva, L.,Bakowski, M.A.,McNamara, C.W.,Catanzaro, N.J.,Graham, R.L.,Schultz, D.C.,Cherry, S.,Kawaoka, Y.,Halfmann, P.J.,Baric, R.S.,Denison, M.R.,Sheahan, T.P.,Sacchettini, J.C. An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo. Cell Rep, 43:114929-114929, 2024 Cited by PubMed Abstract: Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry. NZ-804 potently inhibits SARS-CoV-2 Mpro (0.009 μM IC) as well as SARS-CoV-2 replication in human lung cell lines (0.008 μM EC) and primary human airway epithelial cell cultures. Antiviral activity is maintained against distantly related sarbecoviruses and endemic human CoV OC43. In SARS-CoV-2 mouse and hamster disease models, NZ-804 therapy given once or twice daily significantly diminished SARS-CoV-2 replication and pathogenesis. NZ-804 synthesis is low cost and uncomplicated, simplifying global production and access. These data support the exploration of NZ-804 as a therapy for COVID-19 and future emerging sarbecovirus infections. PubMed: 39504242DOI: 10.1016/j.celrep.2024.114929 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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