{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:36:15Z","timestamp":1790361375258,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,18]],"date-time":"2020-01-18T00:00:00Z","timestamp":1579305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05039"],"award-info":[{"award-number":["16H05039"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: The cationic amphiphilic drug U18666A inhibits the proliferation of type I FIPV in vitro. In this study, we evaluated the in vivo antiviral effects of U18666A by administering it to SPF cats challenged with type I FIPV. Methods: Ten SPF cats were randomly assigned to two experimental groups. FIPV KU-2 were inoculated intraperitoneally to cats. The control group was administered PBS, and the U18666A-treated group was administered U18666A subcutaneously at 2.5 mg\/kg on day 0, and 1.25 mg\/kg on days 2 and 4 after viral inoculation. Results: Two of the five control cats administered PBS alone developed FIP. Four of the five cats administered U18666A developed no signs of FIP. One cat that temporarily developed fever, had no other clinical symptoms, and no gross lesion was noted on an autopsy after the end of the experiment. The FIPV gene was detected intermittently in feces and saliva regardless of the development of FIP or administration of U18666A. Conclusions: When U18666A was administered to cats experimentally infected with type I FIPV, the development of FIP might be suppressed compared with the control group. However, the number of animals with FIP is too low to establish anti-viral effect of U18666A in cats.<\/jats:p>","DOI":"10.3390\/pathogens9010067","type":"journal-article","created":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T04:27:09Z","timestamp":1579494429000},"page":"67","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["In Vivo Antiviral Effects of U18666A Against Type I Feline Infectious Peritonitis Virus"],"prefix":"10.3390","volume":"9","author":[{"given":"Tomoyoshi","family":"Doki","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyo","family":"Tarusawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Hohdatsu","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-0708","authenticated-orcid":false,"given":"Tomomi","family":"Takano","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.tim.2016.03.003","article-title":"Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses","volume":"24","author":"Su","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_2","unstructured":"King, A., Lefkowitz, E., Adams, M.J., and Carstens, E.B. (2012). Order-Nidovirales. Virus Taxonomy, Elsevier."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Whittaker, G.R., Andr\u00e9, N.M., and Millet, J.K. (2018). Improving Virus Taxonomy by Recontextualizing Sequence-Based Classification with Biologically Relevant Data: The Case of the Alphacoronavirus 1 Species. MSphere, 3.","DOI":"10.1128\/mSphereDirect.00463-17"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tekes, G., and Thiel, H.J. (2016). Feline Coronaviruses: Pathogenesis of Feline Infectious Peritonitis. Advances in Virus Research, Academic Press.","DOI":"10.1016\/bs.aivir.2016.08.002"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.virol.2017.12.027","article-title":"Feline coronavirus: Insights into viral pathogenesis based on the spike protein structure and function","volume":"517","author":"Jaimes","year":"2018","journal-title":"Virology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Terada, Y., Matsui, N., Noguchi, K., Kuwata, R., Shimoda, H., Soma, T., Mochizuki, M., and Maeda, K. (2014). Emergence of pathogenic coronaviruses in cats by homologous recombination between feline and canine coronaviruses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106534"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1128\/JVI.01937-08","article-title":"Recombinant Canine Coronaviruses Related to Transmissible Gastroenteritis Virus of Swine Are Circulating in Dogs","volume":"83","author":"Decaro","year":"2009","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1128\/JVI.72.5.4508-4514.1998","article-title":"Feline coronavirus type II strains 79-1683 and 79-1146 originate from a double recombination between feline coronavirus type I and canine coronavirus","volume":"72","author":"Herrewegh","year":"1998","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1099\/vir.0.043992-0","article-title":"Feline infectious peritonitis virus with a large deletion in the 59-terminal region of the spike gene retains its virulence for cats","volume":"93","author":"Terada","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1099\/vir.0.19129-0","article-title":"Persistence and transmission of natural type I feline coronavirus infection","volume":"84","author":"Addie","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_11","first-page":"1209","article-title":"Feline coronavirus serotypes 1 and 2: Seroprevalence and association with disease in Switzerland","volume":"12","author":"Kummrow","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_12","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":"Hohdatsu","year":"1992","journal-title":"J. Vet. Med. Sci."},{"key":"ref_13","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":"Pedersen","year":"2014","journal-title":"Vet. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1177\/1098612X18758592","article-title":"Diagnosis of feline infectious peritonitis: Update on evidence supporting available tests","volume":"20","author":"Tasker","year":"2018","journal-title":"J. Feline Med. Surg."},{"key":"ref_15","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":"Kim","year":"2012","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kim, Y., Liu, H., Galasiti Kankanamalage, A.C., Weerasekara, S., Hua, D.H., Groutas, W.C., Chang, K.O., and Pedersen, N.C. (2016). Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005531"},{"key":"ref_17","doi-asserted-by":"crossref","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":"ref_18","doi-asserted-by":"crossref","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":"ref_19","doi-asserted-by":"crossref","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":"ref_20","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1091\/mbc.12.3.601","article-title":"Dynamic movements of organelles containing Niemann-Pick C1 protein: NPC1 involvement in late endocytic events","volume":"12","author":"Ko","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.antiviral.2011.11.014","article-title":"U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication","volume":"93","author":"Poh","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sabino, C., Basic, M., Bender, D., Elgner, F., Himmelsbach, K., Hildt, E., Sabino, C., Basic, M., Bender, D., and Elgner, F. (2019). Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection. Viruses, 11.","DOI":"10.3390\/v11060524"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1038\/s41598-017-03316-5","article-title":"Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking","volume":"7","author":"Wichit","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11181","DOI":"10.1128\/JVI.01053-16","article-title":"The Intracellular Cholesterol Transport Inhibitor U18666A Inhibits the Exosome-Dependent Release of Mature Hepatitis C Virus","volume":"90","author":"Elgner","year":"2016","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.antiviral.2017.07.022","article-title":"The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection","volume":"145","author":"Takano","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1528-1157.1982.tb06190.x","article-title":"Studies on the Mechanism of the Epileptiform Activity Induced by U18666A. II. Concentration, Half-Life and Distribution of Radiolabeled U18666A in the Brain","volume":"23","author":"Cenedella","year":"1982","journal-title":"Epilepsia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13567-019-0625-3","article-title":"Antiviral activity of itraconazole against type I feline coronavirus infection","volume":"50","author":"Takano","year":"2019","journal-title":"Vet. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1292\/jvms.18-0702","article-title":"Pathogenesis of oral type I feline infectious peritonitis virus (FIPV) infection: Antibody-dependent enhancement infection of cats with type I FIPV via the oral route","volume":"81","author":"Takano","year":"2019","journal-title":"J. Vet. Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1292\/jvms.70.1315","article-title":"Antibody-dependent enhancement occurs upon re-infection with the identical serotype virus in feline infectious peritonitis virus infection","volume":"70","author":"Takano","year":"2008","journal-title":"J. Vet. Med. Sci."},{"key":"ref_30","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":"Pedersen","year":"2015","journal-title":"Vet. Microbiol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/1\/67\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:29:47Z","timestamp":1760362187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/1\/67"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,18]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["pathogens9010067"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9010067","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,18]]}}}