8doy

Crystal structure of SARS-CoV-2 main protease in complex with an inhibitor TKB-198

spinqualitylabelsall models 8doy, resolution 1.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8doy is a 2 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.59Å Ligands: 1PE, DMS, MES, PG0, T1X Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Potent and biostable inhibitors of the main protease (M(pro)) of SARS-CoV-2 were designed and synthesized based on an active hit compound 5h (2). Our strategy was based not only on the introduction of fluorine atoms into the inhibitor molecule for an increase of binding affinity for the pocket of M(pro) and cell membrane permeability but also on the replacement of the digestible amide bond by a surrogate structure to increase the biostability of the compounds. Compound 3 is highly potent and blocks SARS-CoV-2 infection in vitro without a viral breakthrough. The derivatives, which contain a thioamide surrogate in the P2-P1 amide bond of these compounds (2 and 3), showed remarkably preferable pharmacokinetics in mice compared with the corresponding parent compounds. These data show that compounds 3 and its biostable derivative 4 are potential drugs for treating COVID-19 and that replacement of the digestible amide bond by its thioamide surrogate structure is an effective method. Potent and biostable inhibitors of the main protease of SARS-CoV-2.,Tsuji K, Ishii T, Kobayakawa T, Higashi-Kuwata N, Azuma C, Nakayama M, Onishi T, Nakano H, Wada N, Hori M, Shinohara K, Miura Y, Kawada T, Hayashi H, Hattori SI, Bulut H, Das D, Takamune N, Kishimoto N, Saruwatari J, Okamura T, Nakano K, Misumi S, Mitsuya H, Tamamura H iScience. 2022 Nov 18;25(11):105365. doi: 10.1016/j.isci.2022.105365. Epub 2022 , Nov 1. PMID:36338434 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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