Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR “serotyped” (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Background: Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease of cats. Multiple antiviral treatments have been recognized, but optimization of treatment protocols is needed. Objective: To evaluate the efficacy of PO molnupiravir (MPV; EIDD-2801) to treat effusive FIP. Animals: Ten cats with naturally occurring effusive FIP and 10 historical control cats with effusive FIP treated with PO GS-441524. Methods: A single-center, prospective, open-label longitudinal, non-inferiority trial with historical controls. Ten cats with FIP were enrolled and treated with PO MPV (10-15 mg/kg PO q12h) for 84 days. Cats were evaluated at 0, 6, and 16 weeks, and the proportion of cats in clinical remission at 16 weeks was determined. Survival and clinicopathologic features were compared with historical control cats with effusive FIP treated with PO GS-441524. Results: Eight of the 10 cats treated with MPV survived and were in remission at 16 weeks. The 2 non-survivors died in the first 24 hours of treatment. No adverse events that necessitated discontinuation of treatment were observed. Survival of cats treated with PO MPV was non-inferior to historic control cats treated with PO GS-441524 (5/9 [55%] survived), with a difference in survival of 25% (90% confidence interval, −9.3% to 59.3%). Clinicopathologic features associated with FIP normalized during the study period, and no differences in clinicopathologic data at each study time point were observed when comparing cats treated with MPV and GS-441524. Conclusions and Clinical Importance: Molnupiravir is an effective antiviral treatment for effusive FIP.

Feline calicivirus (FCV) is a common cause of upper respiratory infection in cats. Both healthy and infected cells produce small particles called extracellular vesicles (EVs), which are nanoparticles that act as messengers between cells and can be hijacked during viral infection.

Feline infectious peritonitis (FIP) is a devastating and often fatal disease caused by feline coronavirus (FCoV). Currently, there is no widely used vaccine for FIP, and many attempts using a variety of platforms have been largely unsuccessful due to the disease’s highly complicated pathogenesis. One such complication is antibody-dependent enhancement (ADE) seen in FIP, which occurs when sub-neutralizing antibody responses to viral surface proteins paradoxically enhance disease. A novel vaccine strategy is presented here that can overcome the risk of ADE by instead using a lipid nanoparticle-encapsulated mRNA encoding the transcript for the internal structural nucleocapsid (N) FCoV protein. Both wild type and, by introduction of silent mutations, GC content-optimized mRNA vaccines targeting N were developed. mRNA durability in vitro was characterized by quantitative reverse-transcriptase PCR and protein expression by immunofluorescence assay for one week after transfection of cultured feline cells. Both mRNA durability and protein production in vitro were improved with the GC-optimized construct as compared to wild type. Immune responses were assayed by looking at N-specific humoral (by ELISA) and stimulated cytotoxic T cell (by flow cytometry) responses in a proof-of-concept mouse vaccination study. These data together demonstrate that an LNP–mRNA FIP vaccine targeting FCoV N is stable in vitro, capable of eliciting an immune response in mice, and provides justification for beginning safety and efficacy trials in cats.

Objectives: Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus. The nucleoside analog GS-441524, the parent nucleoside of remdesivir, is the most commonly used FIP antiviral. Remdesivir is Food and Drug Administration approved to treat COVID-19 in humans and has been used primarily as an adjunctive treatment for FIP. Data on its efficacy as a first-line oral therapy, as well as its use to treat non-effusive FIP, remain limited. Therefore, this study compares the effectiveness of oral remdesivir vs GS-441524 as a first-line antiviral therapy for cats with non-effusive FIP in a prospective, randomized, double-blind, non-inferiority clinical trial. Furthermore, this study aims to bolster the literature supporting remdesivir use in these cats, anticipating potential future fluctuations in drug cost, availability and legal access. Methods: Cats with non-effusive FIP were randomly assigned to receive either oral remdesivir (38–42 mg/kg, n = 10) or oral GS-441524 (18–22 mg/kg, n = 10) q24h for 84 days (12 weeks). Follow-up was conducted at 6 and 16 weeks, and response to therapy, survival and disease-free remission were assessed. Long-term follow-up was also obtained by contacting owners 1.5–2 years after conclusion of the study. Results: At week 16, 9/10 (90%) cats treated with remdesivir and 7/10 (70%) cats treated with GS-441524 were alive and in clinical remission. Remdesivir met the statistical criteria for non-inferiority, with a difference in disease-free survival of 20% (90% confidence interval –8.5 to +48.5). All deaths during treatment occurred within the first 11 days of the trial. Long-term follow-up revealed new onset of clinical signs and raised concerns for potential late relapse of disease in four cats (two in each group). Conclusions and relevance: This study supports the hypothesis that oral remdesivir is non-inferior to GS-441524 for achieving survival and disease-free remission from FIP at 16 weeks. Given evolving global drug access and costs, remdesivir is a viable first-line option.