Antiviral treatment using the adenosine nucleoside analogue GS‐441524 in cats with clinically diagnosed neurological feline infectious peritonitis

Abstract

Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS‐441524 (5‐10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]‐PCR) and serial ocular imaging using Fourier‐domain optical coherence tomography (FD‐OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS‐441524 shows clinical efficacy and may result in clearance and long‐term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.

Correlation of Feline Coronavirus Shedding in Feces with Coronavirus Antibody Titer

“…For many years, FIP was considered a uniformly fatal disease. Very recently, however, novel drugs, such as a nucleoside analog, GS-441524, were shown to have antiviral efficacy in cats with experimental and natural FIP and in cats with asymptomatic FCoV infection [37][38][39][40]. Nevertheless, these medications are not yet commercially available and might not be affordable for all cat owners, especially for cat breeders and rescue shelters.…”

Subarachnoid diverticulum associated with feline infectious peritonitis in a Siberian cat

“…Recurrence of clinical signs after surgery for SAD has been reported infrequently for both cats and dogs, with the median time from surgery to recurrence of SAD being 20.5 months. 6 In the absence of the experimental antiviral drug GS-441524, prognosis associated with neurological FIP is generally grave, 8 although there are occasional reports of cats surviving clinical FIP. 7 The presence of neurological signs has also been associated with poor response to, or relapse following, initial trial doses of recently described antiviral drugs GC376 and GS-441524, which have been successful in the management of effusive FIP.…”

Current status on treatment options for feline infectious peritonitis and SARS-CoV-2 positive cats

“…Antiviral drugs that inhibit FCoV have been identified but many have not been successfully trialled in infected patients [1,5,14,52,53]. However, a new therapeutic breakthrough using the nucleoside analog GS-441524 as a direct acting antiviral drug for FIP has been reported [19,24,54,55]. GS-441524, the active metabolite of remdesivir, is an RNA-chain terminator of viral RNA dependent RNA polymerase [19,21] and has been found to strongly inhibit FIPV both in tissue culture and experimental cat infection studies as well as in cases of naturally occurring FIP [19,21].…”

“…Based on these findings, the authors A c c e p t e d M a n u s c r i p t concluded that GS-441524 is a safe and effective treatment for FIP when administered at a dosage of 4.0 mg/kg BW SC once a day for at least 12 weeks [21]. A higher dosage of 5.0 to 10.0 mg/kg BW SC once a day for 12 weeks has been recommended for neurological FIP cases as determined by the treatment of four clinical cases [54]. Given the consistency of its reported efficacy, a burgeoning global black-market for GS-441524 has arisen since it has not been formally approved for commercial use anywhere [55].…”