8W1U

SARS-CoV-2 Main protease bound to non-covalent lead molecule NZ-804

これはPDB形式変換不可エントリーです。

8W1U の概要

• エントリーDOI: 10.2210/pdb8w1u/pdb
• 関連するPDBエントリー: 8W1T
• 分子名称: 3C-like proteinase nsp5, 11-[1-(1H-pyrrolo[3,2-c]pyridine-7-carbonyl)piperidin-4-ylidene]-6,11-dihydro-5H-5lambda~6~-dibenzo[b,e]thiepine-5,5-dione, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: protease, inhibitor, complex, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV, COVID-19 virus)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68746.47

構造登録者

Bian, X.,Tang, S.,Sacchettini, J.C. (登録日: 2024-02-18, 公開日: 2024-11-20)

主引用文献

Zhou, N.E.,Tang, S.,Bian, X.,Parai, M.K.,Krieger, I.V.,Flores, A.,Jaiswal, P.K.,Bam, R.,Wood, J.L.,Shi, Z.,Stevens, L.J.,Scobey, T.,Diefenbacher, M.V.,Moreira, F.R.,Baric, T.J.,Acharya, A.,Shin, J.,Rathi, M.M.,Wolff, K.C.,Riva, L.,Bakowski, M.A.,McNamara, C.W.,Catanzaro, N.J.,Graham, R.L.,Schultz, D.C.,Cherry, S.,Kawaoka, Y.,Halfmann, P.J.,Baric, R.S.,Denison, M.R.,Sheahan, T.P.,Sacchettini, J.C.
An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo.
Cell Rep, 43:114929-114929, 2024

PubMed Abstract: Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry. NZ-804 potently inhibits SARS-CoV-2 Mpro (0.009 μM IC) as well as SARS-CoV-2 replication in human lung cell lines (0.008 μM EC) and primary human airway epithelial cell cultures. Antiviral activity is maintained against distantly related sarbecoviruses and endemic human CoV OC43. In SARS-CoV-2 mouse and hamster disease models, NZ-804 therapy given once or twice daily significantly diminished SARS-CoV-2 replication and pathogenesis. NZ-804 synthesis is low cost and uncomplicated, simplifying global production and access. These data support the exploration of NZ-804 as a therapy for COVID-19 and future emerging sarbecovirus infections.

PubMed: 39504242
DOI: 10.1016/j.celrep.2024.114929

実験手法

X-RAY DIFFRACTION (2.05 Å)