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 (3CL pro ) 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 Å X-ray structure of 3CL pro from PEDV. Analysis of the PEDV 3CL pro structure and comparison to other coronaviral 3CL pro ’s from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL pro ’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) 3CL pro , ( R )- 16 , to have inhibitor activity against PEDV 3CL pro , despite that SARS-3CL pro and PEDV 3CL pro share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in ( R )- 16 binding to SARS-3CL pro are conserved in PEDV-3CL pro ; however, the sequence variation and positional difference in the loop forming the S 2 pocket may account for large observed difference in IC 50 values. This work advances our understanding of the subtle, but important, differences in coronaviral 3CL pro architecture and contributes to the broader structural knowledge of coronaviral 3CL pro ’s.
【초록키워드】 Structure, coronavirus, SARS-CoV, knowledge, 3CL pro, protease, virus, X-ray, Phylogeny, mortality rate, inhibitor, expression, binding, epidemic diarrhea, acute respiratory syndrome, residue, PEDV, Coronaviral, purification, sequence variation, sequence identity, infect, conserved, involved, majority, contribute, reveal, alpha-coronavirus, 【제목키워드】 Structure, inhibition,