{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:19:20Z","timestamp":1783955960232,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018065","name":"EveryCat Health Foundation","doi-asserted-by":"crossref","award":["W21-007"],"award-info":[{"award-number":["W21-007"]}],"id":[{"id":"10.13039\/100018065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005595","name":"University of California","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005595","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of California Center for Companion Animal Health","award":["2020-89-FM"],"award-info":[{"award-number":["2020-89-FM"]}]},{"name":"NIH\/NIAID","award":["R21AI159246-01"],"award-info":[{"award-number":["R21AI159246-01"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5K01OD026526"],"award-info":[{"award-number":["5K01OD026526"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Viruses"],"abstract":"<jats:p>Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive (\u201cwet\u201d) form and non-effusive (\u201cdry\u201d) form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and \u03b2-D-N4-hydroxycytidine (NHC; EIDD-1931). These antiviral agents were functionally evaluated using an optimized in vitro bioassay system. Antivirals were assessed as monotherapies against FIPV serotypes I and II and as combined anticoronaviral therapies (CACT) against FIPV serotype II, which provided evidence for synergy for selected combinations. We also determined the pharmacokinetic properties of MPV, GS-441524, and RDV after oral administration to cats in vivo as well as after intravenous administration of RDV. We established that orally administered MPV at 10 mg\/kg, GS-441524 and RDV at 25 mg\/kg, and intravenously administered RDV at 7 mg\/kg achieves plasma levels greater than the established corresponding EC50 values, which are sustained over 24 h for GS-441514 and RDV.<\/jats:p>","DOI":"10.3390\/v14112429","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T03:44:17Z","timestamp":1667360657000},"page":"2429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats"],"prefix":"10.3390","volume":"14","author":[{"given":"Sarah","family":"Cook","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Wittenburg","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0837-5184","authenticated-orcid":false,"given":"Victoria C.","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-0384","authenticated-orcid":false,"given":"Jacob H.","family":"Theil","sequence":"additional","affiliation":[{"name":"Office of Research, Campus Veterinary Services, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Castillo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3426-6352","authenticated-orcid":false,"given":"Krystle L.","family":"Reagan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonyia","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong-Dat","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian L.","family":"Muller","sequence":"additional","affiliation":[{"name":"Sporos Bioventures, @JLABS Suite 201, 2450 Holcombe Blvd, Houston, TX 77021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0057-0604","authenticated-orcid":false,"given":"Brian G.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","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":"Pedersen","year":"2009","journal-title":"Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1006\/viro.1998.9045","article-title":"Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses","volume":"243","author":"Vennema","year":"1998","journal-title":"Virology"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"eabc8413","DOI":"10.1126\/sciimmunol.abc8413","article-title":"The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients","volume":"5","author":"Premkumar","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e00463-17","DOI":"10.1128\/mSphereDirect.00463-17","article-title":"Improving virus taxonomy by recontextualizing sequence-based classification with biologically relevant data: The case of the alphacoronavirus 1 species","volume":"3","author":"Whittaker","year":"2018","journal-title":"MSphere"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jaimes, J.A., Millet, J.K., Stout, A.E., Andr\u00e9, N.M., and Whittaker, G.R. (2020). A tale of two viruses: The distinct spike glycoproteins of feline coronaviruses. Viruses, 12.","DOI":"10.3390\/v12010083"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/030098587200900204","article-title":"Extraperitoneal lesions in feline infectious peritonitis","volume":"9","author":"Montali","year":"1972","journal-title":"Vet. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1939-1676.1998.tb02144.x","article-title":"Diagnostic features of clinical neurologic feline infectious peritonitis","volume":"12","author":"Foley","year":"1998","journal-title":"J. Vet. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jones, S., Novicoff, W., Nadeau, J., and Evans, S. (2021). Unlicensed GS-441524-like antiviral therapy can be effective for at-home treatment of feline infectious peritonitis. Animals, 11.","DOI":"10.3390\/ani11082257"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jfms.2010.09.014","article-title":"Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan","volume":"13","author":"Tsai","year":"2011","journal-title":"J. Feline Med. Surg."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"108398","DOI":"10.1016\/j.vetmic.2019.108398","article-title":"Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor","volume":"237","author":"Perera","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_13","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_14","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_15","doi-asserted-by":"crossref","unstructured":"Krentz, D., Zenger, K., Alberer, M., Felten, S., Bergmann, M., Dorsch, R., Matiasek, K., Kolberg, L., Hofmann-Lehmann, R., and Meli, M.L. (2021). Curing cats with feline infectious peritonitis with an oral multi-component drug containing GS-441524. Viruses, 13.","DOI":"10.3390\/v13112228"},{"key":"ref_16","first-page":"1098612X2110486","article-title":"Investigation of monotherapy and combined anticoronaviral therapies against feline coronavirus serotype II in vitro","volume":"24","author":"Cook","year":"2021","journal-title":"J. Feline Med. Surg."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"e21573","DOI":"10.1096\/fj.202100280RR","article-title":"Potential 3-chymotrypsin-like cysteine protease cleavage sites in the coronavirus polyproteins pp1a and pp1ab and their possible relevance to COVID-19 vaccine and drug development","volume":"35","author":"Yan","year":"2021","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Weiss, S.R., Hughes, S.A., Bonilla, P.J., Turner, J.D., Leibowitz, J.L., and Denison, M.R. (1994). Coronavirus Polyprotein Processing, Springer.","DOI":"10.1007\/978-3-7091-9326-6_35"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5208","DOI":"10.1038\/s41598-021-84754-0","article-title":"A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China","volume":"11","author":"Yin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1021\/acs.jmedchem.0c01929","article-title":"Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models","volume":"65","author":"Li","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1021\/acsmedchemlett.0c00316","article-title":"Advantages of the parent nucleoside GS-441524 over remdesivir for COVID-19 treatment","volume":"11","author":"Yan","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e00221-18","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":"ref_24","doi-asserted-by":"crossref","first-page":"e4166","DOI":"10.1093\/cid\/ciaa1041","article-title":"Remdesivir for severe coronavirus disease 2019 (COVID-19) versus a cohort receiving standard of care","volume":"73","author":"Olender","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/s41467-019-13940-6","article-title":"Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV","volume":"11","author":"Sheahan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.1073\/pnas.1922083117","article-title":"Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection","volume":"117","author":"Feldmann","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","first-page":"1","article-title":"Role of GS-5734 (Remdesivir) in inhibiting SARS-CoV and MERS-CoV: The expected role of GS-5734 (Remdesivir) in COVID-19 (2019-nCoV)-VYTR hypothesis","volume":"11","author":"Yethindra","year":"2020","journal-title":"Int. J. Res. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.36303\/JSAVA.238","article-title":"Successful treatment of a South African cat with effusive feline infectious peritonitis with remdesivir","volume":"93","author":"Bohm","year":"2022","journal-title":"J. S. Afr. Vet. Assoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eaau9242","DOI":"10.1126\/scitranslmed.aau9242","article-title":"Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge","volume":"11","author":"Lo","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"43395","DOI":"10.1038\/srep43395","article-title":"GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses","volume":"7","author":"Lo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","unstructured":"U.S. Food and Drug Administration (2020). FDA Approves First Treatment for COVID-19."},{"key":"ref_32","unstructured":"Malik, R. (2022, July 19). Treatment of FIP in Cats with Subcutaneous Remdesivir Followed by Oral GS-441524 Tablets. Available online: https:\/\/www.zenbycat.org\/blog\/treatment-of-fip-in-cats-with-subcutaneous-remdesivir-followed-by-oral-gs-441524-tablets."},{"key":"ref_33","unstructured":"U.S. Food and Drug Administration (2022, July 19). Fact Sheet for Healthcare Providers: Emergency Use Authorization for Paxlovid, Available online: https:\/\/www.fda.gov\/media\/155050\/download."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/00126334-200202011-00003","article-title":"Pharmacokinetic enhancement of protease inhibitors","volume":"29","author":"Acosta","year":"2002","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/jac\/dkh029","article-title":"Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients","volume":"53","author":"Zeldin","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41586-021-03312-w","article-title":"SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801","volume":"591","author":"Wahl","year":"2021","journal-title":"Nature"},{"key":"ref_37","unstructured":"U.S. National Library of Medicine (2022, August 25). The Safety of Molnupiravir (EIDD-2801) and Its Effect on Viral Shedding of SARS-CoV-2 (END-COVID). Identifier NCT04405739. 28 May 2020\u201321 March 2022, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04405739?id=NCT04405739&draw=2&rank=1&load=cart."},{"key":"ref_38","unstructured":"Warriors, F. (2022, July 19). EIDD-2801. Available online: https:\/\/www.fipwarriors.eu\/en\/eidd-2801-molnupiravir\/."},{"key":"ref_39","first-page":"eabb5883","article-title":"An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus","volume":"12","author":"Sheahan","year":"2020","journal-title":"Biorxiv"},{"key":"ref_40","doi-asserted-by":"crossref","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":"ref_41","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/QAI.0b013e31819675e9","article-title":"The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time","volume":"50","author":"Lima","year":"2009","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1208809","article-title":"Exploratory study of oral combination antiviral therapy for hepatitis C","volume":"368","author":"Poordad","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e263","DOI":"10.1111\/j.1365-2893.2010.01405.x","article-title":"Combined antiviral therapy of hepatitis C virus in dialysis patients: Meta-analysis of clinical trials","volume":"18","author":"Fabrizi","year":"2011","journal-title":"J. Viral Hepat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2018.08.022","article-title":"Characterizing replication kinetics and plaque production of type I feline infectious peritonitis virus in three feline cell lines","volume":"525","author":"Mettelman","year":"2018","journal-title":"Virology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cook, S., Castillo, D., Williams, S., Haake, C., and Murphy, B. (2022). Serotype I and II Feline Coronavirus Replication and Gene Expression Patterns of Feline Cells\u2014Building a Better Understanding of Serotype I FIPV Biology. Viruses, 14.","DOI":"10.3390\/v14071356"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eabc5332","DOI":"10.1126\/scitranslmed.abc5332","article-title":"3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV\u2013infected mice","volume":"12","author":"Rathnayake","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay MethodSynergy Quantification Method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature17180","article-title":"Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys","volume":"531","author":"Warren","year":"2016","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"eaal3653","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":"ref_50","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/cts.12840","article-title":"Safety, tolerability, and pharmacokinetics of remdesivir, an antiviral for treatment of COVID-19, in healthy subjects","volume":"13","author":"Humeniuk","year":"2020","journal-title":"Clin. Transl. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"114356","DOI":"10.1016\/j.jpba.2021.114356","article-title":"The development and validation of a novel LC-MS\/MS method for the simultaneous quantification of Molnupiravir and its metabolite \u00df-d-N4-hydroxycytidine in human plasma and saliva","volume":"206","author":"Amara","year":"2021","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1038\/s41467-020-18096-2","article-title":"Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication","volume":"11","author":"Vuong","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e01719-19","DOI":"10.1128\/AAC.01719-19","article-title":"Analysis of the potential for N 4-hydroxycytidine to inhibit mitochondrial replication and function","volume":"64","author":"Sticher","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.apsb.2021.03.028","article-title":"Can remdesivir and its parent nucleoside GS-441524 be potential oral drugs? An in vitro and in vivo DMPK assessment","volume":"11","author":"Xie","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the Treatment of COVID-19\u2014Final Report","volume":"383","author":"Beigel","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e02428-20","DOI":"10.1128\/AAC.02428-20","article-title":"Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2","volume":"65","author":"Painter","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1136\/bmj.3.5775.607","article-title":"Effect of Age and Sex on Human Drug Metabolism","volume":"3","author":"Crooks","year":"1971","journal-title":"BMJ"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1002\/cbdv.200890214","article-title":"The Biochemistry of Drug Metabolism\u2014An Introduction: Part 6. Inter-Individual Factors Affecting Drug Metabolism","volume":"5","author":"Kraemer","year":"2008","journal-title":"Chem. Biodivers."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/jvp.12717","article-title":"High interindividual variability in plasma clopidogrel active metabolite concentrations in healthy cats is associated with sex and cytochrome P450 2C genetic polymorphism","volume":"42","author":"Lee","year":"2019","journal-title":"J. Vet. Pharmacol. Ther."}],"updated-by":[{"DOI":"10.3390\/v16030397","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000}}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T22:18:06Z","timestamp":1754259486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":59,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["v14112429"],"URL":"https:\/\/doi.org\/10.3390\/v14112429","relation":{"correction":[{"id-type":"doi","id":"10.3390\/v16030397","asserted-by":"object"}]},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}