Human Antiretroviral Drugs Repurposing in the Fight against the Feline Immunodeficiency Virus

Abstract

[Abstract] The feline immunodeficiency virus (FIV), a lentivirus that affects both domestic and wild cats, exhibits structural and pathogenic characteristics similar to those of the human immunodeficiency virus (HIV). This serves as a relevant comparative model for the advancement of antiretroviral drug therapies. Although there have been significant advancements in antiretroviral therapy for HIV, there remains a lack of approved therapeutic strategies for FIV, resulting in a situation where infected cats have no effective treatment options available. This study employed a systematic approach to in silico drug repurposing, incorporating computational screening, pharmacological profiling, and molecular docking followed by molecular dynamics simulation to pinpoint potential inhibitors aimed at key viral proteins. A number of FDA-approved compounds, known for their established safety profiles, exhibited strong binding affinity and favorable pharmacokinetic properties, indicating their potential as candidates for repositioning against FIV. A significant difference in dynamic stability between these compounds was noted based on MD simulation results. Both Paritaprevir and Lenacapavir had high binding scores, as measured by docking, but were subjected to considerable structural fluctuations throughout the course of MD simulation suggesting a lack of long term structure stability. Alternatively, Rilpivirine and Indinavir displayed stability of interaction profiles with favorable energetic properties, and maintained intermolecular interactions, making them promising leads. The results emphasize innovative therapeutic possibilities for veterinary use and offer valuable insights into lentiviral drug development, which could influence future studies in antiviral pharmacology and comparative virology. By connecting veterinary and human pharmaceutical sciences, our study highlights the effectiveness of drug repurposing as a swift and theoretical approach to broadening the antiviral therapeutic landscape. Further experimental validation using in vitro and in vivo studies are required to ensure clinical safety and efficacy in felines.