5EU8

Structure of FIPV main protease in complex with dual inhibitors

Summary for 5EU8

• Entry DOI: 10.2210/pdb5eu8/pdb
• Related PRD ID: PRD_002214
• Descriptor: main protease, N-[(5-METHYLISOXAZOL-3-YL)CARBONYL]ALANYL-L-VALYL-N~1~-((1R,2Z)-4-(BENZYLOXY)-4-OXO-1-{[(3R)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-L-LEUCINAMIDE, ZINC ION, ... (5 entities in total)
• Functional Keywords: fipv, main protease, dual inhibitors, zinc, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Feline infectious peritonitis virus (FIPV); More
• Total number of polymer chains: 2
• Total formula weight: 34305.15

Authors

Wang, F.,Chen, C.,Liu, X.,Yang, K.,Xu, X.,Yang, H. (deposition date: 2015-11-18, release date: 2015-12-30, Last modification date: 2024-11-13)

Primary citation

Wang, F.,Chen, C.,Liu, X.,Yang, K.,Xu, X.,Yang, H.
Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors
J.Virol., 90:1910-1917, 2015

PubMed Abstract: Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases.

PubMed: 26656689
DOI: 10.1128/JVI.02685-15

Experimental method

X-RAY DIFFRACTION (2.447 Å)