9CSY
SARS-CoV-2 papain-like protease (PLpro) bound to PF-07957472
This is a non-PDB format compatible entry.
Summary for 9CSY
| Entry DOI | 10.2210/pdb9csy/pdb |
| Descriptor | Papain-like protease, 2-methyl-5-(4-methylpiperazin-1-yl)-N-{1-[(2P)-2-(1-methyl-1H-pyrazol-4-yl)quinolin-4-yl]cyclopropyl}benzamide, trifluoroacetic acid, ... (5 entities in total) |
| Functional Keywords | papain-like protease, plpro, sars-cov-2 plpro, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 3 |
| Total formula weight | 109469.74 |
| Authors | Mashalidis, E.H.,Chang, J.S.,Wu, H.,Garnsey, M. (deposition date: 2024-07-24, release date: 2024-10-02, Last modification date: 2024-10-30) |
| Primary citation | Garnsey, M.R.,Robinson, M.C.,Nguyen, L.T.,Cardin, R.,Tillotson, J.,Mashalidis, E.,Yu, A.,Aschenbrenner, L.,Balesano, A.,Behzadi, A.,Boras, B.,Chang, J.S.,Eng, H.,Ephron, A.,Foley, T.,Ford, K.K.,Frick, J.M.,Gibson, S.,Hao, L.,Hurst, B.,Kalgutkar, A.S.,Korczynska, M.,Lengyel-Zhand, Z.,Gao, L.,Meredith, H.R.,Patel, N.C.,Polivkova, J.,Rai, D.,Rose, C.R.,Rothan, H.,Sakata, S.K.,Vargo, T.R.,Qi, W.,Wu, H.,Liu, Y.,Yurgelonis, I.,Zhang, J.,Zhu, Y.,Zhang, L.,Lee, A.A. Discovery of SARS-CoV-2 papain-like protease (PL pro ) inhibitors with efficacy in a murine infection model. Sci Adv, 10:eado4288-eado4288, 2024 Cited by PubMed Abstract: Vaccines and first-generation antiviral therapeutics have provided important protection against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PL) is one of the two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease have demonstrated clinical efficacy, known PL inhibitors have, to date, lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PL translates to in vivo efficacy in a preclinical setting. Here, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PL inhibitors, with lead compound PF-07957472 () providing robust efficacy in a mouse-adapted model of COVID-19 infection. PubMed: 39213347DOI: 10.1126/sciadv.ado4288 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.595 Å) |
Structure validation
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