11ROSummary for 11RO
| Entry DOI | 10.2210/pdb11ro/pdb |
| Related PRD ID | PRD_002602 |
| Descriptor | 3C-like proteinase nsp5, N-(trifluoroacetyl)-D-phenylalanyl-N-{(1Z,2S)-1-imino-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-L-phenylalaninamide (3 entities in total) |
| Functional Keywords | mpro, sars2, coronavirus, viral protease, main protease, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 |
| Total number of polymer chains | 2 |
| Total formula weight | 68196.65 |
| Authors | Shaqra, A.M.,Adnan, S.F.Z.,Lee, L.T.,Iyer, V.,Jung, K.,Intravaia, L.E.,Kaur, J.,Schiffer, C.A. (deposition date: 2026-03-10, release date: 2026-04-22, Last modification date: 2026-10-07) |
| Primary citation | Barasa, L.,Chen, Y.,Shaqra, A.M.,Adnan, S.F.Z.,Intravaia, L.E.,Huchaiah, S.,Allabaji, A.,S, K.K.,Vidadala, S.R.,Patil, S.N.,Hale, J.,Schiffer, C.A.,Fitzgerald, K.A.,Thompson, P.R. Nitrile-Based Inhibitors Targeting both SARS-CoV‐2 Main Protease and Human Cathepsin L. Acs Med.Chem.Lett., 17:1956-1965, 2026 Cited by PubMed Abstract: The SARS-CoV-2 main protease (M) and host cysteine protease cathepsin L (CatL) are both attractive targets for antiviral intervention. Herein we describe the rational design and synthesis of dual M/CatL inhibitors derived from the previously reported leads and . Optimization focused on replacement of the acrylate ester warhead in and with a nitrile, modifying the P2, P3, and P4 capping groups, and variation of the P1 lactam ring size. In addition, conformational restriction was achieved through macrocyclization between the P1 and P4 side chains to enhance binding affinity. These efforts identified multiple dual-target inhibitors with nanomolar potency against both M and CatL and potent antiviral activity as well as selective M inhibitors with strong enzymatic activity. Targeting both a viral protease and a host factor may provide more durable antiviral efficacy by reducing susceptibility to resistance arising from viral evolution of M. PubMed: 42741323DOI: 10.1021/acsmedchemlett.6c00236 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.71 Å) |
Structure validation
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