Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur
Open Access
- 7 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 27 (6), 529-532
- https://doi.org/10.1038/s41594-020-0440-6
Abstract
The antineoplastic drug carmofur is shown to inhibit the SARS-CoV-2 main protease (Mpro). Here, the X-ray crystal structure of Mpro 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 (EC50 = 24.30 μM) and is a promising lead compound to develop new antiviral treatment for COVID-19.This publication has 22 references indexed in Scilit:
- The newly emerged SARS-Like coronavirus HCoV-EMC also has an “Achilles’ heel”: current effective inhibitor targeting a 3C-like proteaseProtein & Cell, 2013
- Towards automated crystallographic structure refinement with phenix.refineActa Crystallographica Section D-Biological Crystallography, 2012
- Features and development of CootActa Crystallographica Section D-Structural Biology, 2010
- XDSActa Crystallographica Section D-Structural Biology, 2010
- Structures of Two Coronavirus Main Proteases: Implications for Substrate Binding and Antiviral Drug DesignJournal of Virology, 2008
- Phasercrystallographic softwareJournal of Applied Crystallography, 2007
- Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main ProteasesPLoS Biology, 2005
- An Individual Patient Data Meta-analysis of Adjuvant Therapy with Carmofur in Patients with Curatively Resected Colon CancerJapanese Journal of Clinical Oncology, 2005
- Plasma, Intestine and Tumor Levels of 5-Fluorouracil in Mice Bearing L1210 Ascites Tumor Following Oral Administration of 5-Fluorouracil, UFT (Mixed Compound of Tegafur and Uracil), Carmofur and 5'-Deoxy-5-fluorouridine.Biological & Pharmaceutical Bulletin, 2001
- Oral Carmofur in Advanced Gastrointestinal CancerAmerican Journal of Clinical Oncology, 1990