GS-443902 and Feline-Infectious-Peritonitis

Feline infectious peritonitis (FIP) is a mysterious and lethal disease of cats. The causative agent, feline coronavirus (FCoV), is ubiquitous in most feline populations, yet the disease is sporadic in nature. Mutations in the infecting virus combined with an inappropriate immune response to the FCoV contribute to the development of FIP. Diagnosis can be challenging because signs may be vague, clinical pathology parameters are nonspecific, and the gold standard for diagnosis is invasive: histopathology of affected tissue. This article discusses the developments in the understanding of this disease as well as the progress in diagnosis and treatment.

Topics: Adenosine Triphosphate; Animals; Antiviral Agents; Cats; Coronavirus, Feline; Feline Infectious Peritonitis; Genetic Predisposition to Disease; Pyrrolidines; Sulfonic Acids

Topics: Adenosine Triphosphate; Amodiaquine; Angiotensin-Converting Enzyme 2; Animals; Antiviral Agents; Betacoronavirus; Cats; Central Nervous System; Coronavirus Infections; Coronavirus, Feline; COVID-19; COVID-19 Drug Treatment; Feline Infectious Peritonitis; Humans; Nelfinavir; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protease Inhibitors; Pyrrolidines; SARS-CoV-2; Sulfonic Acids

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.

Topics: Adenosine Triphosphate; Animals; Antiviral Agents; Cats; Feline Infectious Peritonitis; Female; Male