Zhenming Jin, Yao Zhao, Yuanyuan Sun
May 7, 2020
Citations
15
Influential Citations
315
Citations
Quality indicators
Journal
Nature Structural & Molecular Biology
Abstract
The antineoplastic drug carmofur is shown to inhibit the SARS-CoV-2 main protease (M pro ). Here, the X-ray crystal structure of M pro in complex with carmofur reveals that the carbonyl reactive group of carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC 50 = 24.30 μM) and is a promising lead compound to develop new antiviral treatment for COVID-19. A crystal structure of SARS-CoV-2 with inhibitor carmofur reveals the mechanism of action of this compound and opens the way to develop more potent drugs.