Background: Feline immunodeficiency virus (FIV) remains one of the most important chronic viral infections affecting domestic cats, yet the therapeutic landscape for FIV has developed more slowly than that for many human viral diseases. The references provided for the present article span antiviral pharmacology, herpesvirus treatment experience in feline and human ophthalmic disease, structural studies of FIV proteolytic processing, feline lentiviral protease inhibition, antiviral assembly targeting, and host restriction mechanisms. When examined together, these studies offer a useful basis for understanding how antiviral development for FIV can be approached in a mechanistically coherent way.

Objective: This article aimed to generate a publication-ready integrative research synthesis assessing the efficacy and therapeutic promise of antiviral strategies relevant to FIV, with particular emphasis on protease inhibition, viral assembly disruption, and host-directed restriction approaches, while also drawing conceptual lessons from established antiviral treatment paradigms in herpesvirus infections.

Methodology: A qualitative integrative review design was used. The included references were analyzed through a structured thematic framework covering antiviral principles, translational lessons from feline herpesvirus and herpes simplex therapy, FIV molecular processing targets, protease inhibitor design, retroviral assembly inhibition, and innate or synthetic host restriction strategies. Evidence was interpreted comparatively, with attention to mechanism of action, translational value, potential resistance concerns, and clinical applicability.

Results: The reviewed literature indicates that the most compelling FIV-directed antiviral evidence centers on protease biology and protease inhibition. Identification of gag and pol processing sites established the molecular basis for rational drug targeting (Elder et al., 1993). Subsequent substrate specificity analyses enabled development of broad-based inhibitors active against FIV, simian immunodeficiency virus, and human immunodeficiency virus in vitro and ex vivo (Lee et al., 1998). Therapeutic benefit in an in vivo disease context was supported by TL-3–mediated prevention and resolution of neurological deficits in FIV infection (Huitron-Resendiz et al., 2004). Response patterns to tipranavir further suggested the value of FIV as a comparative model for drug-resistant retroviral protease inhibition (Norelli et al., 2008). Additional conceptual promise was identified in capsid assembly targeting, antiviral interference with virion morphogenesis, and synthetic feline TRIM5-CypA restriction systems (Neira, 2009; Prevelige, 2011; Dietrich et al., 2010; Dietrich et al., 2011; Towers, 2007). Lessons from herpesvirus therapy underscore the importance of mechanism-specific intervention, timely treatment, and resistance-aware drug development (De Clercq, 2004; James and Prichard, 2014; Stiles, 1995; Thomasy et al., 2016; Luntz and MacCallum, 1963; Kaufman, 1980).

Conclusion: Current evidence supports a strategically layered model for FIV treatment in which protease inhibition remains the strongest direct antiviral approach, while assembly inhibitors and host-directed restriction strategies represent important next-generation directions. Progress in FIV therapeutics will depend on integrating molecular precision, feline-specific pharmacologic evaluation, and resistance-conscious combination design.

feline immunodeficiency virus, antiviral therapy, protease inhibitors

De Clercq, E. (2004). Antivirals and antiviral strategies. Nature Reviews Microbiology, 2, 704–720.

Dietrich, I., Macintyre, A., McMonagle, E., Price, A. J., James, L. C., McEwan, W. A., Hosie, M. J., & Willett, B. J. (2010). Potent lentiviral restriction by a synthetic feline TRIM5 cyclophilin A fusion. Journal of Virology, 84, 8980–8985.

Dietrich, I., McEwan, W. A., Hosie, M. J., & Willett, B. J. (2011). Restriction of the felid lentiviruses by a synthetic feline TRIM5-CypA fusion. Veterinary Immunology and Immunopathology, 143, 235–242.

Elder, J. H., Schnolzer, M., Hasselkus-Light, C. S., Henson, M., Lerner, D. A., Phillips, T. R., Wagaman, P. C., & Kent, S. B. (1993). Identification of proteolytic processing sites within the gag and pol polyproteins of feline immunodeficiency virus. Journal of Virology, 67, 1869–1876.

Huitron-Resendiz, S., de Rozieres, S., Sanchez-Alavez, M., Buhler, B., Lin, Y. C., Lerner, D. L., Henriksen, N. W., Burudi, M., Fox, H. S., Torbett, B. E., & others. (2004). Resolution and prevention of feline immunodeficiency virus-induced neurological deficits by treatment with the protease inhibitor TL-3. Journal of Virology, 78, 4525–4532.

James, S. H., & Prichard, M. N. (2014). Current and future therapies for herpes simplex virus infections: Mechanism of action and drug resistance. Current Opinion in Virology, 8, 54–61.

Kaufman, H. E. (1980). Antimetabolite drug therapy in herpes simplex. Ophthalmology, 87, 135–139.

Lee, T., Laco, G. S., Torbett, B. E., Fox, H. S., Lerner, D. L., Elder, J. H., & Wong, C. H. (1998). Analysis of the S3 and S3’ subsite specificities of feline immunodeficiency virus protease: Development of a broad-based protease inhibitor efficacious against FIV, SIV, and HIV in vitro and ex vivo. Proceedings of the National Academy of Sciences of the United States of America, 95, 939–944.

Luntz, M. H., & MacCallum, F. O. (1963). Treatment of herpes simplex keratitis with 5-iodo-2'-deoxyuridine. British Journal of Ophthalmology, 47, 449–456.

Neira, J. L. (2009). The capsid protein of human immunodeficiency virus: Designing inhibitors of capsid assembly. FEBS Journal, 276, 6110–6117.

Norelli, S., El Daker, S., D’Ostilio, D., Mele, F., Mancini, F., Taglia, F., Ruggieri, A., Ciccozzi, M., Cauda, R., Ciervo, A., & others. (2008). Response of feline immunodeficiency virus to tipranavir may provide new clues for development of broad-based inhibitors of retroviral proteases acting on drug-resistant HIV-1. Current HIV Research, 6, 306–317.

Prevelige, P. E., Jr. (2011). New approaches for antiviral targeting of HIV assembly. Journal of Molecular Biology, 410, 634–640.

Stiles, J. (1995). Treatment of cats with ocular disease attributable to herpesvirus infection: 17 cases (1983–1993). Journal of the American Veterinary Medical Association, 207, 599–603.

Thomasy, S. M., Shull, O., Outerbridge, C. A. L., et al. (2016). Oral administration of famciclovir for treatment of spontaneous ocular, respiratory or dermatologic disease attributed to feline herpesvirus type-1: A retrospective review in 59 client-owned cats. Journal of the American Veterinary Medical Association.

Towers, G. J. (2007). The control of viral infection by tripartite motif proteins and cyclophilin A. Retrovirology, 4