{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:42:03Z","timestamp":1791859323153,"version":"4.3.4"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2016,3,30]],"date-time":"2016-03-30T00:00:00Z","timestamp":1459296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1005531","type":"journal-article","created":{"date-parts":[[2016,3,30]],"date-time":"2016-03-30T22:04:23Z","timestamp":1459375463000},"page":"e1005531","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":190,"title":["Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor"],"prefix":"10.1371","volume":"12","author":[{"given":"Yunjeong","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushka C.","family":"Galasiti Kankanamalage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahani","family":"Weerasekara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duy H.","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Groutas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong-Ok","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels C.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,3,30]]},"reference":[{"key":"ref1","article-title":"Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses","author":"AM King","year":"2011"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-3527(08)60286-9","article-title":"The molecular biology of coronaviruses","volume":"48","author":"MM Lai","year":"1997","journal-title":"Adv Virus Res"},{"issue":"7","key":"ref3","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1128\/JVI.06540-11","article-title":"Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus","volume":"86","author":"PC Woo","year":"2012","journal-title":"J Virol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.coviro.2014.06.002","article-title":"Antiviral drugs specific for coronaviruses in preclinical development","volume":"8","author":"AO Adedeji","year":"2014","journal-title":"Curr Opin Virol"},{"issue":"10","key":"ref5","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1517\/13543776.2013.823159","article-title":"Anti-SARS coronavirus agents: a patent review (2008\u2014present)","volume":"23","author":"V Kumar","year":"2013","journal-title":"Expert Opin Ther Pat"},{"issue":"2","key":"ref6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1586\/14787210.4.2.291","article-title":"Potential antivirals and antiviral strategies against SARS coronavirus infections","volume":"4","author":"E De Clercq","year":"2006","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"18","key":"ref7","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1111\/febs.12936","article-title":"From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design","volume":"281","author":"R Hilgenfeld","year":"2014","journal-title":"FEBS J"},{"issue":"10","key":"ref8","doi-asserted-by":"crossref","first-page":"e324","DOI":"10.1371\/journal.pbio.0030324","article-title":"Design of wide-spectrum inhibitors targeting coronavirus main proteases","volume":"3","author":"H Yang","year":"2005","journal-title":"PLoS Biol"},{"issue":"Pt 11","key":"ref9","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1099\/0022-1317-71-11-2599","article-title":"Porcine respiratory coronavirus differs from transmissible gastroenteritis virus by a few genomic deletions","volume":"71","author":"D Rasschaert","year":"1990","journal-title":"J Gen Virol"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jfms.2008.09.008","article-title":"A review of feline infectious peritonitis virus infection: 1963\u20132008","volume":"11","author":"NC Pedersen","year":"2009","journal-title":"J Feline Med Surg"},{"issue":"2","key":"ref11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.tvjl.2014.04.017","article-title":"An update on feline infectious peritonitis: Virology and immunopathogenesis","volume":"201","author":"NC Pedersen","year":"2014","journal-title":"Veterinary Journal"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virusres.2011.12.020","article-title":"Feline infectious peritonitis: role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats","volume":"165","author":"NC Pedersen","year":"2012","journal-title":"Virus Res"},{"issue":"2","key":"ref13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3390\/v1020166","article-title":"Significance of coronavirus mutants in feces and diseased tissues of cats suffering from feline infectious peritonitis","volume":"1","author":"NC Pedersen","year":"2009","journal-title":"Viruses"},{"issue":"7","key":"ref14","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.3201\/eid1807.120143","article-title":"Spike protein fusion Peptide and feline coronavirus virulence","volume":"18","author":"HW Chang","year":"2012","journal-title":"Emerg Infect Dis"},{"issue":"3","key":"ref15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/jvim.12058","article-title":"Phylogenetic analysis of feline coronavirus strains in an epizootic outbreak of feline infectious peritonitis","volume":"27","author":"EN Barker","year":"2013","journal-title":"J Vet Intern Med"},{"issue":"7","key":"ref16","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.3201\/eid1907.121094","article-title":"Mutation in spike protein cleavage site and pathogenesis of feline coronavirus","volume":"19","author":"BN Licitra","year":"2013","journal-title":"Emerg Infect Dis"},{"issue":"2\u20134","key":"ref17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.vetmic.2014.10.025","article-title":"Levels of feline infectious peritonitis virus in blood, effusions, and various tissues and the role of lymphopenia in disease outcome following experimental infection","volume":"175","author":"NC Pedersen","year":"2015","journal-title":"Vet Microbiol"},{"issue":"Suppl 4","key":"ref18","first-page":"21","article-title":"Mechanisms of lymphocyte loss in SARS coronavirus infection","volume":"14","author":"PK Chan","year":"2008","journal-title":"Hong Kong Med J"},{"issue":"2\u20134","key":"ref19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.vetmic.2006.08.033","article-title":"A &quot;possible&quot; involvement of TNF-alpha in apoptosis induction in peripheral blood lymphocytes of cats with feline infectious peritonitis","volume":"119","author":"T Takano","year":"2007","journal-title":"Vet Microbiol"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.virol.2007.02.006","article-title":"TNF-alpha, produced by feline infectious peritonitis virus (FIPV)-infected macrophages, upregulates expression of type II FIPV receptor feline aminopeptidase N in feline macrophages","volume":"364","author":"T Takano","year":"2007","journal-title":"Virology"},{"issue":"1\u20132","key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetmic.2003.08.010","article-title":"In vivo cytokine response to experimental feline infectious peritonitis virus infection","volume":"97","author":"GA Dean","year":"2003","journal-title":"Vet Microbiol"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1128\/JVI.79.2.1036-1044.2005","article-title":"Natural history of a recurrent feline coronavirus infection and the role of cellular immunity in survival and disease","volume":"79","author":"JD de Groot-Mijnes","year":"2005","journal-title":"J Virol"},{"issue":"6","key":"ref23","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/j.1939-1676.2007.tb01937.x","article-title":"Effect of feline interferon-omega on the survival time and quality of life of cats with feline infectious peritonitis","volume":"21","author":"S Ritz","year":"2007","journal-title":"J Vet Intern Med"},{"issue":"6","key":"ref24","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1111\/j.1939-1676.2011.00806.x","article-title":"Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis","volume":"25","author":"Y Fischer","year":"2011","journal-title":"J Vet Intern Med"},{"issue":"2","key":"ref25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.tvjl.2014.04.016","article-title":"An update on feline infectious peritonitis: Diagnostics and therapeutics","volume":"201","author":"NC Pedersen","year":"2014","journal-title":"Veterinary Journal"},{"issue":"7","key":"ref26","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.2460\/javma.2001.218.1111","article-title":"Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals","volume":"218","author":"BW Rohrbach","year":"2001","journal-title":"J Am Vet Med Assoc"},{"issue":"5","key":"ref27","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1128\/JVI.64.5.1964-1972.1990","article-title":"Prevalence and implications of feline coronavirus infections of captive and free-ranging cheetahs (Acinonyx jubatus)","volume":"64","author":"JL Heeney","year":"1990","journal-title":"J Virol"},{"issue":"21","key":"ref28","doi-asserted-by":"crossref","first-page":"11754","DOI":"10.1128\/JVI.01348-12","article-title":"Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and coronaviruses","volume":"86","author":"Y Kim","year":"2012","journal-title":"J Virol"},{"issue":"2","key":"ref29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.antiviral.2012.11.005","article-title":"Potent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like protease","volume":"97","author":"Y Kim","year":"2013","journal-title":"Antiviral Res"},{"issue":"9","key":"ref30","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1128\/JVI.03688-14","article-title":"Broad-spectrum inhibitors against 3C-Like proteases of feline coronaviruses and feline caliciviruses","volume":"89","author":"Y Kim","year":"2015","journal-title":"J Virol"},{"issue":"20","key":"ref31","doi-asserted-by":"crossref","first-page":"11825","DOI":"10.1128\/JVI.01749-14","article-title":"A chimeric virus-mouse model system for evaluating the function and inhibition of papain-like proteases of emerging coronaviruses","volume":"88","author":"X Deng","year":"2014","journal-title":"J Virol"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.virol.2011.12.002","article-title":"Characterization and inhibition of norovirus proteases of genogroups I and II using a fluorescence resonance energy transfer assay","volume":"423","author":"KO Chang","year":"2012","journal-title":"Virology"},{"issue":"2","key":"ref33","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0006-291X(67)80055-X","article-title":"On the size of the active site in proteases. I. Papain","volume":"27","author":"I Schechter","year":"1967","journal-title":"Biochem Biophys Res Commun"},{"issue":"1\u20132","key":"ref34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.vetimm.2014.09.001","article-title":"The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis","volume":"162","author":"NC Pedersen","year":"2014","journal-title":"Vet Immunol Immunopathol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s12917-014-0186-7","article-title":"An eight-year epidemiologic study based on baculovirus-expressed type-specific spike proteins for the differentiation of type I and II feline coronavirus infections","volume":"10","author":"YT Wang","year":"2014","journal-title":"BMC Vet Res"},{"issue":"10","key":"ref36","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1128\/CDLI.12.10.1209-1215.2005","article-title":"Feline coronavirus serotypes 1 and 2: seroprevalence and association with disease in Switzerland","volume":"12","author":"M Kummrow","year":"2005","journal-title":"Clin Diagn Lab Immunol"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.vetmic.2003.07.010","article-title":"Prevalence of feline coronavirus types I and II in cats with histopathologically verified feline infectious peritonitis","volume":"99","author":"V Benetka","year":"2004","journal-title":"Vet Microbiol"},{"issue":"3","key":"ref38","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1292\/jvms.54.557","article-title":"The prevalence of types I and II feline coronavirus infections in cats","volume":"54","author":"T Hohdatsu","year":"1992","journal-title":"J Vet Med Sci"},{"issue":"6","key":"ref39","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"TD Schmittgen","year":"2008","journal-title":"Nat Protoc"},{"issue":"Pt 5","key":"ref40","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1107\/S1399004715003521","article-title":"Structures of the Middle East respiratory syndrome coronavirus 3C-like protease reveal insights into substrate specificity","volume":"71","author":"D Needle","year":"2015","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.bmc.2014.12.028","article-title":"Fused-ring structure of decahydroisoquinolin as a novel scaffold for SARS 3CL protease inhibitors","volume":"23","author":"Y Shimamoto","year":"2015","journal-title":"Bioorg Med Chem"},{"issue":"2","key":"ref42","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1128\/JVI.02576-13","article-title":"Inhibition of NF-kappaB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival","volume":"88","author":"ML DeDiego","year":"2014","journal-title":"J Virol"},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.virol.2009.09.023","article-title":"A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo","volume":"395","author":"CW Day","year":"2009","journal-title":"Virology"},{"issue":"21","key":"ref44","doi-asserted-by":"crossref","first-page":"11416","DOI":"10.1128\/JVI.01410-12","article-title":"Intranasal treatment with poly(I*C) protects aged mice from lethal respiratory virus infections","volume":"86","author":"J Zhao","year":"2012","journal-title":"J Virol"},{"issue":"5626","key":"ref45","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1126\/science.1085658","article-title":"Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs","volume":"300","author":"K Anand","year":"2003","journal-title":"Science"},{"issue":"20","key":"ref46","doi-asserted-by":"crossref","first-page":"5684","DOI":"10.1016\/j.bmcl.2008.08.082","article-title":"Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors","volume":"18","author":"AK Ghosh","year":"2008","journal-title":"Bioorg Med Chem Lett"},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"7646","DOI":"10.1074\/jbc.M807947200","article-title":"Structural basis of inhibition specificities of 3C and 3C-like proteases by zinc-coordinating and peptidomimetic compounds","volume":"284","author":"CC Lee","year":"2009","journal-title":"J Biol Chem"},{"issue":"23","key":"ref48","doi-asserted-by":"crossref","first-page":"13190","DOI":"10.1073\/pnas.1835675100","article-title":"The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor","volume":"100","author":"H Yang","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ref49","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2174\/156802606776287090","article-title":"Characterization and inhibition of SARS-coronavirus main protease","volume":"6","author":"PH Liang","year":"2006","journal-title":"Curr Top Med Chem"},{"issue":"3","key":"ref50","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.febslet.2008.12.059","article-title":"Individual and common inhibitors of coronavirus and picornavirus main proteases","volume":"583","author":"CJ Kuo","year":"2009","journal-title":"FEBS Lett"},{"issue":"16","key":"ref51","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1021\/jm0603926","article-title":"Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor","volume":"49","author":"S Yang","year":"2006","journal-title":"Journal of Medicinal Chemistry"},{"issue":"20","key":"ref52","doi-asserted-by":"crossref","first-page":"11886","DOI":"10.1128\/JVI.01528-14","article-title":"Coronaviruses resistant to a 3C-like protease inhibitor are attenuated for replication and pathogenesis, revealing a low genetic barrier but high fitness cost of resistance","volume":"88","author":"X Deng","year":"2014","journal-title":"J Virol"},{"issue":"23","key":"ref53","doi-asserted-by":"crossref","first-page":"6317","DOI":"10.1016\/j.bmcl.2013.09.070","article-title":"Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors","volume":"23","author":"AM Prior","year":"2013","journal-title":"Bioorg Med Chem Lett"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.vetimm.2016.01.002","article-title":"Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection","volume":"171","author":"NC Pedersen","year":"2016","journal-title":"Veterinary Immunology and Immunopathology"},{"issue":"52","key":"ref55","article-title":"Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency","author":"S Beaucourt","year":"2011","journal-title":"Jove-J Vis Exp"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/1756-0500-3-226","article-title":"EasyModeller: A graphical interface to MODELLER","volume":"3","author":"BK Kuntal","year":"2010","journal-title":"BMC Res Notes"},{"key":"ref57","unstructured":"The PyMOL Molecular Graphics System VS, LLC."}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1005650","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T00:00:00Z","timestamp":1462924800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1005531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T23:49:31Z","timestamp":1600386571000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1005531"}},"subtitle":[],"editor":[{"given":"Stanley","family":"Perlman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,3,30]]},"references-count":57,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1005531","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.ppat.1005650","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,30]]}}}