{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T09:15:54Z","timestamp":1793870154869,"version":"4.6.1"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The main objectives of this study were to investigate the efficacy of the nucleotide analog GS-441524 in combination with the 3C-like protease inhibitor GC376 for the treatment of naturally aquired feline infectious peritonitis (FIP) and to test whether their combination shortens the dosing period and improves the cure rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 46 FIP-affected cats were enrolled in this experiment, including 36 with wet FIP (29 with abdominal effusion, six with thoracic effusion, and one with thoracic+abdominal effusion), and 10 with dry FIP. The cats were aged from 3 to 96 months. Thoracic+abdominal effusion, lymph-node puncture fluid and perirenal puncture fluid was collected from the affected cats for qPCR testing, and all 46 cats were positive for feline coronavirus (FCoV). The cats divided into different dose groups, all treated for 4 weeks: group 1 (GS-441524, 5 mg\/kg.sc.q.24 h; GC376, 20 mg\/kg.sc.q.12 h), group 2 (GS-441524, 2.5 mg\/kg.sc.q.24 h; GC376, 20 mg\/kg.sc.q.12 h), group 3 (GS-441524, 2.5 mg\/kg.sc.q.24 h; GC376, 10 mg\/kg.sc.q.12 h), and group 4 (GS-441524, 5 mg\/kg.sc.q.24 h; GC376, 10 mg\/kg.sc.q.12 h).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After the 4-week combination treatment, 45 of the 46 (97.8%) cats survived, and 43 of those became clinically normal. Two cats required longer (7 to 12 weeks) treatment to achieve full recovery. As of writing (10 months after completion of the trial), all 45 cats were alive and no relapse was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and relevance<\/jats:title><jats:p>GS-441524 combined with GC376 can be safely and effectively used to treat FIP and reduces the treatment period to 4 weeks, with an excellent cure rate.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2022.1002488","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T09:22:50Z","timestamp":1666948970000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Effect of GS-441524 in combination with the 3C-like protease inhibitor GC376 on the treatment of naturally transmitted feline infectious peritonitis"],"prefix":"10.3389","volume":"9","author":[{"given":"Jinbao","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipeng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1007\/s00705-015-2370-x","article-title":"Differential effects of viroporin inhibitors against feline infectious peritonitis virus serotypes I and II","volume":"160","author":"Takano","year":"2015","journal-title":"Arch Virol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1111\/tbed.13856","article-title":"Feline infectious peritonitis (FIP) and coronavirus disease 19 (COVID-19): are they similar?","volume":"68","author":"Paltrinieri","year":"2021","journal-title":"Transbound Emerg Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.jfms.2008.09.008","article-title":"A review of feline infectious peritonitis virus infection: 1963-2008","volume":"11","author":"Pedersen","year":"2009","journal-title":"J Feline Med Surg."},{"key":"B4","doi-asserted-by":"publisher","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":"Rohrbach","year":"2001","journal-title":"Javma-J Am Vet Med A."},{"key":"B5","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.tvjl.2014.04.017","article-title":"An update on feline infectious peritonitis: virology and immunopatho- genesis","volume":"201","author":"Pedersen","year":"2014","journal-title":"Vet J"},{"key":"B6","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/S0165-2427(98)00158-5","article-title":"Cellular composition, coronavirus antigen expression and production of specific antibodies in lesions in feline infectious peritoniti","volume":"65","author":"Kipar","year":"1998","journal-title":"Vet Immunol Immunop"},{"key":"B7","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1177\/1098612X17729626","article-title":"Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis","volume":"20","author":"Pedersen","year":"2018","journal-title":"J Feline Med Surg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1177\/1098612X19825701","article-title":"Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis","volume":"21","author":"Pedersen","year":"2019","journal-title":"J Feline Med Surg"},{"key":"B9","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.vetmic.2018.04.026","article-title":"The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies","volume":"219","author":"Murphy","year":"2018","journal-title":"Vet Microbiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1099\/vir.0.016485-0","article-title":"Feline infectious peritonitis: insights into feline coronavirus pathobiogenesis and epidemiology based on genetic analysis of the viral 3c gene","volume":"91","author":"Chang","year":"2010","journal-title":"J Gen Virol."},{"key":"B11","doi-asserted-by":"publisher","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":"Kim","year":"2012","journal-title":"J Virol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scitranslmed.aal3653","article-title":"Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses","volume":"9","author":"Sheahan","year":"2017","journal-title":"Sci Transl Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1111\/jvim.15780","article-title":"Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis","volume":"34","author":"Dickinson","year":"2020","journal-title":"J Vet Intern Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1016\/j.bmcl.2012.02.105","article-title":"Synthesis and antiviral activity of a series of 1'-substituted 4-aza-7,9-dideazaadenosine C-nucleosides","volume":"22","author":"Cho","year":"2012","journal-title":"Bioorg Med Chem Lett."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.3390\/v11111068","article-title":"Diagnosis of feline infectious peritonitis: a review of the current literature","volume":"11","author":"Felten","year":"2019","journal-title":"Viruses"},{"key":"B16","doi-asserted-by":"publisher","first-page":"4609","DOI":"10.1021\/cr010184f","article-title":"Viral proteases","volume":"102","author":"Tong","year":"2002","journal-title":"Chem Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e324","DOI":"10.1371\/journal.pbio.0030324","article-title":"Design of wide-spectrum inhibitors targeting coronavirus main proteases","volume":"3","author":"Yang","year":"2005","journal-title":"PLoS Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1005531","DOI":"10.1371\/journal.ppat.1005531","article-title":"Reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor","volume":"12","author":"Kim","year":"2016","journal-title":"PLoS Pathog."},{"key":"B19","doi-asserted-by":"publisher","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":"de Groot-Mijnes","year":"2005","journal-title":"J Virol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e00221","DOI":"10.1128\/mBio.00221-18","article-title":"Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease","volume":"9","author":"Agostini","year":"2018","journal-title":"MBio."},{"key":"B21","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1046\/j.1440-1711.2000.00933.x","article-title":"Restraining mycobacteria-Role of granulomas in mycobacterial infections","volume":"78","author":"Bernadette","year":"2000","journal-title":"Immunol Cell Biol."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.1002488\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T09:22:52Z","timestamp":1666948972000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.1002488\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,28]]},"references-count":21,"alternative-id":["10.3389\/fvets.2022.1002488"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2022.1002488","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,28]]},"article-number":"1002488"}}