# Efficacy of GS-441524 for Feline Infectious Peritonitistis: A Systematic Review (2018-2024)
## 1 Introduction  
Feline infectious peritonitis (FIP) is a devastating disease caused by certain strains of feline coronavirus (FCoV) that acquire mutations leading to a virulent biotype (FIPV) [1]. Among FCoV-infected cats, only a small proportion develop FIP [2], which occurs primarilyin young cats (3 months to 2 years old) and in cats from multi-cat environments like shelters or catteries, where FCoV exposure is high [2,3].  
FIPV, unlike the benign feline enteric coronavirus (FECV), has a higher tropism for monocytes and macrophages, disseminating through lymphatic and vascular systems and causing a systemic disease [1]. Clinically, FIP manifests in two forms: effusive FIP, characterized by immune-mediated vasculitis and effusions in body cavities; and non-effusive FIP, characterized by granulomatous lesions in various organs. These forms can overlap. [4]. Despite being recognized since 1963, FIP has historically carried a near-100% fatality rate in cats that develop the disease [5].  
Diagnosing FIP is challenging. In 2022, the AAFP/EveryCat Foundation published comprehensive FIP diagnostic guidelines [5]. A presumptive FIP diagnosis is based on the cat's age, history, clinical signs (Figure 1), and consistent laboratory findings (e.g., cytology of effusions, hematology, and biochemistry) [2]. A confirmatory diagnosis requires a combination of the latter alongside positive PCR and immunohistochemistry [5].  
Without antiviral therapy, FIP is almost invariably fatal--affected cats typically deteriorate and die or are euthanized within weeks [6]. Historically, only palliative treatments (e.g., NSAIDs, immunomodulators like interferons, and supportive care) were available, which did not cure the disease [6].  
In recent years, new antiviral molecules have given hope for treating FIP. One of the most promising is GS-441524, an adenosine nucleoside analogue that inhibits the RNA-dependent RNA polymerase of coronavirus and causes premature termination of viral RNA synthesis [7]. Another antiviral that was explored is GC376, a 3C-like protease inhibitor which prevents maturation of viral polyproteins and thereby inhibits viral replication [1]. Also of note is GS-5734 (Remdesivir), the prodrug of GS-441524, which is metabolized into GS-441524 in vivo and has similar antiviral effects [8]. Molnupiravir (EIDD-2801) is yet another antiviral that has been investigated more recently for FIP, particularly as a rescue therapy in GS-441524-resistant cases [9].  
Despite the success of these antivirals in research settings, GS-441524 itself is not currently approved globally as a veterinary drug. Gilead Sciences holds the patent for GS-441524 and has not authorized its veterinary use, meaning veterinarians and cat owners have resorted to black-market sources of GS-441524 in the past. They can now obtain it through licenced compounding pharmacies, which have been made available in many countries. It is legally available via veterinary \"channels\" in Australia, Canada, the Netherlands, the UK, and the USA as a compounded treatment. BOVA, a UK-based company supplying veterinary pharmaceuticals, supplies it in this form. The human drug Remdesivir (which is licenced for COVID-19) has been legally used as an alternative in some places (e.g., under veterinary cascade or compassionate use) [10]. The increasing use of GS-441524 in the field has dramatically improved FIP outcomes and lowered the disease's lethality rate [7]. Nonetheless, concerns remain about the emergence of drug-resistant viral mutants, suboptimal drug distribution to certain sites (e.g., brain), and potential adverse effects of these treatments [1,11].  
This review aims to systematically synthesize the literature on FIP treatment with GS-441524. Specifically, we evaluate the efficacy of GS-441524 (alone or combined with other antivirals/immunomodulators) on the survival and remission of cats with FIP, stratified by FIP form (effusive, non-effusive, mixed), presence of severe clinical signs (e.g., neurological or ocular involvement), and route of administration used.