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Title: X-ray structure and inhibition of 3C-like protease from porcine epidemic diarrhea virus

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep25961· OSTI ID:1283059
 [1];  [2];  [1]
  1. Purdue Univ., West Lafayette, IN (United States). Dept. of Chemistry, Dept. of Biological Sciences, Centers for Cancer Research & Drug Discovery
  2. Purdue Univ., West Lafayette, IN (United States). Dept. of Biological Sciences
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Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CLpro) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 angstrom X-ray structure of 3CLpro from PEDV. Analysis of the PEDV 3CLpro structure and comparison to other coronaviral 3CLpro's from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CLpro's are conserved, with the exception of a loop that comprises the protease S-2 pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro, (R)-16, to have inhibitor activity against PEDV 3CLpro, despite that SARS-3CLpro and PEDV 3CLpro share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CLpro are conserved in PEDV-3CLpro; however, the sequence variation and positional difference in the loop forming the S-2 pocket may account for large observed difference in IC50 values. In conclusion, this work advances our understanding of the subtle, but important, differences in coronaviral 3CLpro architecture and contributes to the broader structural knowledge of coronaviral 3CLpro's.

Research Organization:
Purdue Univ., West Lafayette, IN (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1283059
Journal Information:
Scientific Reports, Vol. 6; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

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Cited By (1)

Porcine Epidemic Diarrhea Virus 3C-Like Protease-Mediated Nucleocapsid Processing: Possible Link to Viral Cell Culture Adaptability journal November 2016

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
coronavirus main proteinase
cov 3cl protease
3clpro
design
drug discovery
x-ray crystallography