From ebola to feline infectious peritonitis: the cross-species journey of GS-441524 and the future of antiviral translation

Abstract

The feline coronavirus treatment GS-441524 represents a unique case of translational medicine in reverse: a compound developed for a rare human disease, abandoned in human clinical use, but successfully repurposed to treat a fatal veterinary condition affecting cats. Initially designed as a nucleoside analog for the Ebola virus, GS-441524 underwent preclinical safety testing in animals before being discovered to have unexpected clinical applications in feline infectious peritonitis (FIP), a historically untreatable disease in cats caused by a virulent systemic feline coronavirus (FCoV). This review traces the scientific and regulatory journey of GS-441524 from human antiviral candidate to life-saving feline treatment. We also expand the discussion to include the emerging use of other human antivirals, such as molnupiravir, in veterinary medicine. Ethical and public health tensions created by unregulated, community-driven drug access are examined, alongside the broader One Health implications, including antiviral resistance and the lack of surveillance in non-human hosts. Finally, we explore how lessons from FIP treatment may inform human medicine, particularly in the context of long COVID and future coronavirus pandemics. This translational scenario exemplifies both the potential and the pitfalls of cross-species drug translation, underscoring the need for integrated regulatory and ethical frameworks to support responsible innovation.

Keywords

Veterinary / feline medicine / remdesivir / infectious disease

References

[1] Negash R,Li E,Jacque N,Novicoff W,Evans SJM. Owner experience and veterinary involvement with unlicensed GS-441524 treatment of feline infectious peritonitis: a prospective cohort study Front Vet Sci. 2024 11 1377207 PMC11233523

[2] Yates MK,Seley-radtke KL. The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: complex modifications to the nucleoside scaffold Antiviral Res. 2019 162 5 21 PMC6349489

[3] Jordheim LP,Durantel D,Zoulim F,Dumontet C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases Nat Rev Drug Discov. 2013 12 447 64

[4] Rasmussen HB,Thomsen R,Hansen PR. Nucleoside analog GS‐441524: pharmacokinetics in different species, safety, and potential effectiveness against Covid‐19 Pharmacol Res Perspect. 2022 10 e00945 PMC8994193

[5] Gordon CJ,Walker SM,Tchesnokov EP.et al. Mechanism and spectrum of inhibition of a 4’-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses J Biol Chem. 2024 300 107514

[6] Coggins S,Cerna P. Pharmacologic approaches to feline infectious peritonitis. Today’s Veterinary Practice. 2025. Available from: https://todaysveterinarypractice.com/pharmacology/pharmacologic-approaches-to-feline-infectious-peritonitis/ [Last accessed on 8 Jun 2026]

[7] Agostini ML,Andres EL,Sims AC.et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) Is mediated by the viral polymerase and the proofreading exoribonuclease mBio 2018 9 e00221 18

[8] Rasmussen HB,Jürgens G,Thomsen R.et al. Cellular uptake and intracellular phosphorylation of GS-441524: implications for its effectiveness against COVID-19 Viruses 2021 13 1369 PMC8310262

[9] Siegel D,Hui HC,Doerffler E.et al. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses J Med Chem. 2017 60 1648 61

[10] Yan VC,Muller FL. Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment ACS Med Chem Lett. 2020 11 1361 6 PMC7315846

[11] Clercq ED. Antivirals and antiviral strategies Nat Rev Microbiol. 2004 2 704 20 PMC7097272

[12] Warren TK,Jordan R,Lo MK.et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys Nature. 2016 531 381 5

[13] Sheahan TP,Sims AC,Graham RL.et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses Sci Transl Med. 2017 9 eaal3653 PMC5567817

[14] Holzworth J. Some important disorders of cats Cornell Vet. 1963 53 157 60

[15] Pedersen NC. A review of feline infectious peritonitis virus infection: 1963-2008 J Feline Med Surg. 2009 11 225 58

[16] Kent MS,Karchemskiy S,Culp WTN.et al. Longevity and mortality in cats: a single institution necropsy study of 3108 cases (1989-2019) PLoS ONE. 2022 17 e0278199

[17] Pedersen NC. Serologic studies of naturally occurring feline infectious peritonitis Am J Vet Res. 1976 37 1449 54

[18] Tasker S,Addie DD,Egberink H.et al. Feline infectious peritonitis: european advisory board on cat diseases guidelines Viruses. 2023 15 1847 PMC10535984

[19] Kipar A,May H,Menger S,Weber M,Leukert W,Reinacher M. Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis Vet Pathol. 2005 42 321 30

[20] Legendre AM,Kuritz T,Galyon G,Baylor VM,Heidel RE. Polyprenyl immunostimulant treatment of cats with presumptive non-effusive feline infectious peritonitis in a field study Front. Vet. Sci. 2017 4 PMC5306384

[21] Fischer Y,Ritz S,Weber K,Sauter-louis C,Hartmann K. Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis J Vet Intern Med. 2011 25 1270 6 PMC7166892

[22] Ritz S,Egberink H,Hartmann K. Effect of feline interferon-omega on the survival time and quality of life of cats with feline infectious peritonitis J Vet Intern Med. 2007 21 1193 7

[23] Santoro MG,Carafoli E. Remdesivir: from ebola to COVID-19 Biochem Biophys Res Commun. 2021 538 145 50 PMC7836944

[24] World Health Organization. Ebola Outbreak 2014-2016 - West Africa. Ebola Virus Disease: Situation Report. Available from: https://www.who.int/emergencies/situations/ebola-outbreak-2014-2016-West-Africa [Last accessed on 8 Jun 2026]

[25] Mulangu S,Dodd LE,Davey RT.et al. A randomized, controlled trial of ebola virus disease therapeutics N Engl J Med. 2019 381 2293 303

[26] GILEAD. Gilead donates remdesivir for Ebola Clinical Trial in the Democratic Republic of the Congo. 2025. Available from: https://www.gilead.com/company/company-statements/2025/gilead-donates-remdesivir-for-ebola-clinical-trial-in-the-democratic-republic-of-the-congo [Last accessed on 8 Jun 2026]

[27] Brown AJ,Won JJ,Graham RL.et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase Antiviral Res. 2019 169 104541 PMC6699884

[28] Murphy BG,Perron M,Murakami E. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies Vet Microbiol. 2018 219 226 33 PMC7117434

[29] Pedersen NC,Perron M,Bannasch M.et al. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis J Feline Med Surg. 2019 21 271 81

[30] Coggins SJ,Norris JM,Malik R.et al. Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS-441524 J Vet Intern Med. 2023 37 1772 83 PMC10473006

[31] Cosaro E,Pires J,Castillo D,Murphy BG,Reagan KL. Efficacy of oral remdesivir compared to GS-441524 for treatment of cats with naturally occurring effusive feline infectious peritonitis: a blinded, non-inferiority study Viruses. 2023 15 1680 PMC10458979

[32] Green J,Syme H,Tayler S. Thirty-two cats with effusive or non-effusive feline infectious peritonitis treated with a combination of remdesivir and GS-441524 J Vet Intern Med. 2023 37 1784 93 PMC10472986

[33] Dickinson PJ,Bannasch M,Thomasy SM.et al. Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis J Vet Intern Med. 2020 34 1587 93 PMC7379040

[34] Krentz D,Zenger K,Alberer M.et al. Curing cats with feline infectious peritonitis with an oral multi-component drug containing GS-441524 Viruses. 2021 13 2228 PMC8621566

[35] Gordon CJ,Tchesnokov EP,Woolner E.et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency J Biol Chem. 2020 295 6785 97

[36] Choy K,Wong AY,Kaewpreedee P.et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro Antiviral Res. 2020 178 104786 PMC7127386

[37] Eastman RT,Roth JS,Brimacombe KR.et al. Remdesivir: a review of its discovery and development leading to emergency use authorization for treatment of COVID-19 ACS Cent. Sci. 2020 6 672 83 PMC7202249

[38] Chua K,Conti RM. Policy implications of the orphan drug designation for remdesivir to treat COVID-19 JAMA Intern Med. 2020 180 1273

[39] Spinner CD,Gottlieb RL,Criner GJ.et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial JAMA 2020 324 1048 57

[40] Wang Y,Zhang D,Du G.et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Lancet. 2020 395 1569 78

[41] Sarpatwari A,Kaltenboeck A,Kesselheim AS. Missed opportunities on emergency remdesivir use JAMA 2020 324 331

[42] Bhimraj A,Morgan RL,Shumaker AH.et al. Infectious diseases society of america guidelines on the treatment and management of patients with COVID-19 (September 2022) Clin Infect Dis. 2024 78 e250 349 PMC9494372

[43] Jones S,Novicoff W,Nadeau J,Evans S. Unlicensed GS-441524-like antiviral therapy can be effective for at-home treatment of feline infectious peritonitis Animals. 2021 11 2257 PMC8388366

[44] Guidance for industry - small entities compliance guide - designation of new animal drugs for minor uses or minor species. Available from: https://www.fda.gov/media/79363/download [Last accessed on 8 Jun 2026]

[45] Roy M,Jacque N,Novicoff W,Li E,Negash R,Evans SJM. Unlicensed molnupiravir is an effective rescue treatment following failure of unlicensed GS-441524-like therapy for cats with suspected feline infectious peritonitis Pathogens. 2022 11 1209 PMC9612227

[46] Office UA, Oregon D of. January 27, 2025. 2025. Federal law enforcement seizes $4 million in property and proceeds from Texas Woman for smuggling and distributing unapproved animal drugs. Available from: https://www.justice.gov/usao-or/pr/federal-law-enforcement-seizes-4-million-property-and-proceeds-texas-woman-smuggling-and [Last accessed on 8 Jun 2026]

[47] Kent AM,Guan S,Jacque N,Novicoff W,Evans SJM. Unlicensed antiviral products used for the at-home treatment of feline infectious peritonitis contain GS-441524 at significantly different amounts than advertised J Am Vet Med Assoc. 2024 262 489 97 PMC11983332

[48] FDA Announces position on use of compounded GS-441524 to treat FIP. 2024. Available from: https://www.fda.gov/animal-veterinary/cvm-updates/fda-announces-position-use-compounded-gs-441524-treat-fip [Last accessed on 8 Jun 2026]

[49] Compounding animal drugs from bulk drug substances: guidance for industry. 2022. Available from: https://www.fda.gov/media/132567/download?attachment [Last accessed on 8 Jun 2026]

[50] Rollin BE. An ethicist’s commentary on extra-label drug use Can Vet J. 2002 43 749 50

[51] Wong CKH,Lau KTK,Au ICH,Xiong X,Lau EHY,Cowling BJ. Clinical improvement, outcomes, antiviral activity, and costs associated with early treatment with remdesivir for patients with coronavirus disease 2019 (COVID-19) Clin Infect Dis. 2022 74 1450 8 PMC8406861

[52] Finn A,Jindal A,Andrea SB,Selvaraj V,Dapaah-afriyie K. Association of treatment with remdesivir and 30-day hospital readmissions in patients hospitalized with COVID-19 Am J Med Sci. 2022 363 403 10 PMC8830144

[53] Sanderson T,Hisner R,Donovan-banfield I.et al. A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes Nature. 2023 623 594 600 PMC10651478

[54] Tempestilli M,Caputi P,Avataneo V.et al. Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19 J Antimicrob Chemother. 2020 75 2977 80

[55] Greenhalgh T, Sivan M, Perlowski A, Nikolich JŽ. Long COVID: a clinical update Lancet. 2024 404 707 24

[56] Wanakumjorn P,Kimura K,Castillo D.et al. Mesenchymal stem/stromal cell therapy improves immune recovery in a feline model of severe coronavirus infection Stem Cells Transl Med. 2025 14 szaf025 PMC12259234

[57] Zhang S. A much-hyped COVID-19 drug is almost identical to a black-market cat cure. The Atlantic. 2020. Available from: https://www.theatlantic.com/science/archive/2020/05/remdesivir-cats/611341/ [Last accessed on 8 Jun 2026]

[58] Ciortea D,Matei MN,Debita M.et al. Cardiac manifestations and emerging biomarkers in multisystem inflammatory syndrome in children (MIS-C): a systematic review and meta-analysis Life. 2025 15 805 PMC12113149

[59] Reardon S. New NIH office to reduce use of animals in research. Science. 2025. Available from: https://www.science.org/content/article/new-nih-office-reduce-use-animals-research [Last accessed on 8 Jun 2026]

[60] Attipa C,Warr AS,Epaminondas D.et al. Emergence and spread of feline infectious peritonitis due to a highly pathogenic canine/feline recombinant coronavirus bioRxiv. 2024 2023.11.08.566182

[61] Olarte-Castillo XA,Choi A,Frazier LE,Whittaker G. Rethinking the drivers of coronavirus virulence and pathogenesis: toward an understanding of the dynamic world of mutations, indels, and recombination within the species alphacoronavirus-1. 2024

[62] Cook S,Wittenburg L,Yan VC.et al. 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 Viruses. 2022 14 2429

[63] Sase O. Molnupiravir treatment of 18 cats with feline infectious peritonitis: a case series J Vet Intern Med. 2023 37 1876 80 PMC10472991

[64] Reagan KL,Brostoff T,Pires J,Rose A,Castillo D,Murphy BG. Open label clinical trial of orally administered molnupiravir as a first-line treatment for naturally occurring effusive feline infectious peritonitis J Vet Intern Med. 2024 38 3087 94 PMC11586577

[65] Černá P,Wittenburg L,Hawley J,Willis M,Siegenthaler B,Lappin MR. Pharmacokinetics of molnupiravir in cats with naturally occurring feline infectious peritonitis Pathogens. 2025 14 666 PMC12299796

[66] Clark T,Coggins S,Korman R,King J,Malik R. Treatment of feline infectious peritonitis in cats with molnupiravir: clinical observations and outcomes for 54 cases Aust Vet J. 2025 103 339 53

[67] Allinder M,Tynan B,Martin C.et al. Uroliths composed of antiviral compound GS-441524 in 2 cats undergoing treatment for feline infectious peritonitis J Vet Intern Med. 2024 38 370 4 PMC10800210

[68] Nomah DK,Reyes-urueña J,Llibre JM.et al. HIV and SARS-CoV-2 Co-infection: epidemiological, clinical features, and future implications for clinical care and public health for people living with HIV (PLWH) and HIV most-at-risk groups Curr HIV/AIDS Rep. 2022 19 17 25 PMC8810339