8UIF

Crystal structure of SARS CoV-2 3CL protease in complex with GSK4365096A

This is a non-PDB format compatible entry.

Summary for 8UIF

• Entry DOI: 10.2210/pdb8uif/pdb
• Descriptor: 3C-like proteinase nsp5, N-[(benzyloxy)carbonyl]-4-fluoro-L-phenylalanyl-N-{(2R)-1-[(2S)-oxolan-2-yl]-3-[(3S)-2-oxooxolan-3-yl]propan-2-yl}-L-leucinamide (3 entities in total)
• Functional Keywords: 3cl protease, sars, viral protein, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 2
• Total formula weight: 68902.55

Authors

Concha, N.O.,Williams, S.P. (deposition date: 2023-10-10, release date: 2024-02-14)

Primary citation

Barton, L.S.,Callahan, J.F.,Cantizani, J.,Concha, N.O.,Cotillo Torrejon, I.,Goodwin, N.C.,Joshi-Pangu, A.,Kiesow, T.J.,McAtee, J.J.,Mellinger, M.,Nixon, C.J.,Padron-Barthe, L.,Patterson, J.R.,Pearson, N.D.,Pouliot, J.J.,Rendina, A.R.,Buitrago Santanilla, A.,Schneck, J.L.,Sanz, O.,Thalji, R.K.,Ward, P.,Williams, S.P.,King, B.W.
Exploration of the P1 residue in 3CL protease inhibitors leading to the discovery of a 2-tetrahydrofuran P1 replacement.
Bioorg.Med.Chem., 100:117618-117618, 2024

PubMed Abstract: The virally encoded 3C-like protease (3CL) is a well-validated drug target for the inhibition of coronaviruses including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Most inhibitors of 3CL are peptidomimetic, with a γ-lactam in place of Gln at the P1 position of the pseudopeptide chain. An effort was pursued to identify a viable alternative to the γ-lactam P1 mimetic which would improve physicochemical properties while retaining affinity for the target. Discovery of a 2-tetrahydrofuran as a suitable P1 replacement that is a potent enzymatic inhibitor of 3CL in SARS-CoV-2 virus is described herein.

PubMed: 38309201
DOI: 10.1016/j.bmc.2024.117618

Experimental method

X-RAY DIFFRACTION (2.02 Å)