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dc.contributor.authorPerera, Krishani Dinali
dc.contributor.authorRathnayake, Athri D.
dc.contributor.authorLiu, Hongwei
dc.contributor.authorPedersen, Niels C.
dc.contributor.authorGroutas, William C.
dc.contributor.authorChang, Kyeong-Ok
dc.contributor.authorKim, Yunjeong
dc.date.accessioned2019-09-13T21:43:08Z
dc.date.available2019-09-13T21:43:08Z
dc.date.issued2019-10
dc.identifier.citationPerera, Krishani Dinali; Rathnayake, Athri D.; Liu, Hongwei; Pedersen, Niels C.; Groutas, William C.; Chang, Kyeong-Ok; Kim, Yunjeong. 2019. Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor. Veterinary Microbiology, vol. 237, October 2019, art. no. 108398en_US
dc.identifier.urihttp://doi.org/10.1016/j.vetmic.2019.108398
dc.identifier.urihttp://hdl.handle.net/10057/16587
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractFeline infectious peritonitis (FIP) is a highly fatal disease caused by a virulent feline coronavirus in domestic and wild cats. We have previously reported the synthesis of potent coronavirus 3C-like protease (3CLpro) inhibitors and the efficacy of a protease inhibitor, GC376, in client-owned cats with FIP. In this study, we studied the effect of the amino acid changes in 3CLpro of feline coronavirus from a feline patient who received antiviral treatment for prolonged duration. We generated recombinant 3CLpro containing the identified amino acid changes (N25S, A252S or K260 N) and determined their susceptibility to protease inhibitors in the fluorescence resonance energy transfer assay. The assay showed that N25S in 3CLpro confers a small change (up to 1.68-fold increase in the 50% inhibitory concentration) in susceptibility to GC376, but other amino acid changes do not affect susceptibility. Modelling of 3CLpro carrying the amino acid changes was conducted to probe the structural basis for these findings. The results of this study may explain the observed absence of clinical resistance to the long-term antiviral treatment in the patients.en_US
dc.description.sponsorshipNational Institutes of Health , grant number R01 AI130092 , and Morris Animal Foundation , grant numbers D14FE-012 and D16FE-512.en_US
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesVeterinary Microbiology;v.237:art. no.108398
dc.subjectFeline infectious peritonitis virusen_US
dc.subject3C-like proteaseen_US
dc.subjectAntiviralsen_US
dc.subjectGenetic barrieren_US
dc.subjectFeline coronavirusen_US
dc.subjectResistanceen_US
dc.titleCharacterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitoren_US
dc.typeArticleen_US
dc.rights.holder© 2019 Elsevier B.V.en_US


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