6Y2E
Crystal structure of the free enzyme of the SARS-CoV-2 (2019-nCoV) main protease
Summary for 6Y2E
| Entry DOI | 10.2210/pdb6y2e/pdb |
| Descriptor | 3C-like proteinase (2 entities in total) |
| Functional Keywords | novel coronavirus, alpha-ketoamide, antiviral, drug design, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) |
| Total number of polymer chains | 1 |
| Total formula weight | 33825.55 |
| Authors | Zhang, L.,Sun, X.,Hilgenfeld, R. (deposition date: 2020-02-15, release date: 2020-03-04, Last modification date: 2024-01-24) |
| Primary citation | Zhang, L.,Lin, D.,Sun, X.,Curth, U.,Drosten, C.,Sauerhering, L.,Becker, S.,Rox, K.,Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors. Science, 368:409-412, 2020 Cited by PubMed Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (M, also called 3CL) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 M and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 M The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route. PubMed: 32198291DOI: 10.1126/science.abb3405 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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