Potent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like protease

dc.citation.doi10.1016/j.antiviral.2012.11.005en_US
dc.citation.epage168en_US
dc.citation.issue2en_US
dc.citation.jtitleAntiviral Researchen_US
dc.citation.spage161en_US
dc.citation.volume97en_US
dc.contributor.authorKim, Yunjeong
dc.contributor.authorMandadapu, Sivakoteswara Rao
dc.contributor.authorGroutas, William C.
dc.contributor.authorChang, Kyeong-Ok
dc.contributor.authoreidykimen_US
dc.contributor.authoreidkchangen_US
dc.date.accessioned2013-04-18T16:07:38Z
dc.date.available2013-04-18T16:07:38Z
dc.date.issued2013-02-01
dc.date.published2013en_US
dc.description.abstractFeline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against a feline coronavirus in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC[subscript 50] in a nanomolar range) and, furthermore, the combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in a cell culture system.en_US
dc.identifier.urihttp://hdl.handle.net/2097/15525
dc.language.isoen_USen_US
dc.relation.urihttp://www.doi.org/10.1016/j.antiviral.2012.11.005en_US
dc.subjectFeline coronavirusesen_US
dc.subjectFeline infectious peritonitis virusen_US
dc.subjectProtease inhibitoren_US
dc.subjectCathepsin Ben_US
dc.subjectSynergyen_US
dc.subject3CL proteaseen_US
dc.titlePotent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like proteaseen_US
dc.typeArticle (author version)en_US

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