8Y44

Crystal structure of SARS-CoV-2 3CL protease (3CLpro) in complex with compound 44

これはPDB形式変換不可エントリーです。

8Y44 の概要

• エントリーDOI: 10.2210/pdb8y44/pdb
• 分子名称: 3C-like proteinase nsp5, ~{N}-[(1~{S},2~{R})-2-[(4-bromanyl-2-morpholin-4-ylcarbonyl-6-nitro-phenyl)amino]cyclohexyl]-2-oxidanylidene-1~{H}-quinoline-4-carboxamide (3 entities in total)
• 機能のキーワード: mpro, viral protein-inhibitor complex, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68847.98

構造登録者

Nie, T.Q.,Su, H.X.,Li, M.J.,Xu, Y.C. (登録日: 2024-01-30, 公開日: 2025-02-12, 最終更新日: 2025-03-26)

主引用文献

Jiang, Z.,Feng, B.,Chen, L.,Nie, T.,Chen, S.,Wang, L.,Liu, H.,Yu, T.,Zhang, Y.,Zheng, M.,Xu, Y.,Liu, H.,Zang, Y.,Su, H.,Zhang, L.,Li, J.,Zhou, Y.
Discovery of Novel Nonpeptidic and Noncovalent Small Molecule 3CL pro Inhibitors as anti-SARS-CoV-2 Drug Candidate.
J.Med.Chem., 67:12760-12783, 2024

PubMed Abstract: SARS-CoV-2 has still been threatening global public health with its emerging variants. Our previous work reported lead compound that displayed good 3CL inhibitory activity. Here, an in-depth structural optimization for was launched to obtain more desirable drug candidates for the therapy of SARS-CoV-2 infection, in which 54 novel derivatives were designed and synthesized by a structure-based drug design strategy. Among them, 24 compounds show significantly enhanced 3CL inhibitory potencies with IC values less than 100 nM, and 11 compounds dose-dependently inhibit the replication of the SARS-CoV-2 delta variant. In particular, compound has the most desirable antiviral activity with EC of 0.272 ± 0.013 μM against the delta variant, which was more than 20 times stronger than . Oral administration of could significantly reduce the lung viral copies of mice, exhibiting a more favorable therapeutic potential. Overall, this investigation presents a promising drug candidate for further development to treat SARS-CoV-2 infection.

PubMed: 39072488
DOI: 10.1021/acs.jmedchem.4c00739

実験手法

X-RAY DIFFRACTION (1.91 Å)