9IPP

Crystal structure of MERS main protease in complex with carmofur

Summary for 9IPP

• Entry DOI: 10.2210/pdb9ipp/pdb
• Descriptor: 3C-like proteinase, hexylcarbamic acid (3 entities in total)
• Functional Keywords: viral protein-inhibitor complex, viral protein
• Biological source: Middle East respiratory syndrome-related coronavirus
• Total number of polymer chains: 2
• Total formula weight: 65795.32

Authors

Guo, L.,Zhou, X.L.,Zeng, P.,Li, W.W.,Zhang, J.,Li, J. (deposition date: 2024-07-11, release date: 2025-07-16, Last modification date: 2026-01-28)

Primary citation

Guo, L.,Zeng, P.,Zhou, X.,Li, W.,Zhang, J.,Li, J.
Structural basis of main proteases of MERS-CoV bound to antineoplastic drug carmofur.
Biochem.Biophys.Res.Commun., 735:150469-150469, 2024

PubMed Abstract: Recurrent epidemics of coronaviruses have posed significant threats to human life and health. The mortality rate of patients infected with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is 35 %. The main protease (M) plays a crucial role in the MERS-CoV life cycle, and M exhibited a high degree of conservation among different coronaviruses. Therefore inhibition of M has become an effective strategy for the development of broad-spectrum anti-coronaviral drugs. The inhibition of SARS-CoV-2 M by the anti-tumor drug carmofur has been revealed, but structural studies of carmofur in complex with M from other types of coronavirus have not been reported. Hence, we revealed the structure of the MERS-CoV M-carmofur complex, analysed the structural basis for the binding of carmofur to MERS-CoV M in detail, and compared the binding patterns of carmofur to Ms of two different coronaviruses, MERS-CoV and SARS-CoV-2. Considering the importance of Ms for coronavirus therapy, structural understanding of M inhibition by carmofur could contribute to the design and development of novel antiviral drugs with safe and broad-spectrum efficacy.

PubMed: 39106601
DOI: 10.1016/j.bbrc.2024.150469

Experimental method

X-RAY DIFFRACTION (2.26 Å)