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Feline infectious peritonitis (FIP) is caused by infection with the feline coronavirus (FCoV) and is fatal if left untreated. In most cats, FCoV primarily infects the gastrointestinal tract and remains asymptomatic or causes only mild enteritis, with only a small proportion of infected cats developing FIP. An excessive and harmful immune response leading to characteristic (pyo)granulomatous phlebitis is believed to play a key role in the development of FIP, along with complex interactions between host and viral factors. Our research group recently demonstrated successful treatment of cats with naturally occurring FIP using the antiviral nucleoside analogue GS-441524. Treatment led to complete recovery without any relapses for a follow-up period of one year, demonstrating both a short- and long-term cure. To investigate differential gene expression and corresponding molecular pathways in cats with FIP before, during, and after antiviral treatment, RNA sequencing was performed on full blood samples of 18 cats treated successfully in a prospective study. Samples were analyzed before treatment, at different timepoints while on treatment with GS-441524 and after completion of treatment. Additionally, gene expression profiles were compared to 12 healthy FCoV-infected control cats and 5 healthy uninfected control cats. The results revealed both a widespread dysregulation of the blood RNA signature in cats with FIP as well as its rapid normalization within the first week of treatment. Significant changes were already apparent within the first two days of treatment. The results of the present study suggest that elimination of the virus from the blood leads to rapid control and subsequent normalization of the damaging immune response, a finding that corresponds well to the clinical response to treatment. This study illustrates the host response to treatment at the molecular level and provides further evidence that a shorter treatment duration than the 84 days predominantly practiced is sufficient.

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.

Background GS‐441524 has been successfully used to treat feline infectious peritonitis (FIP) in cats. However, the use of its prodrug, remdesivir, in combination with a PO GS‐441524 containing product for the treatment of FIP has not yet been described. Objectives Describe treatment protocols, response to treatment and outcomes in cats with FIP treated with a combination of PO GS‐441524 and injectable remdesivir. Animals Thirty‐two client‐owned cats diagnosed with effusive or non‐effusive FIP including those with ocular and neurological involvement. Methods Cats diagnosed with FIP at a single university hospital between August 2021 and July 2022 were included. Variables were recorded from time of diagnosis, and subsequent follow‐up information was obtained from the records of referring veterinarians. All surviving cats were observed for the entire 12‐week treatment period. Results Cats received treatment with different combinations of IV remdesivir, SC remdesivir, and PO GS‐441524 at a median (range) dosage of 15 (10‐20) mg/kg. Clinical response to treatment was observed in 28 of 32 cats (87.5%) in a median (range) of 2 (1‐5) days. Twenty‐six of 32 cats (81.3%) were alive and in clinical and biochemical remission at the end of the 12‐week treatment period. Six of 32 cats (18.8%) died or were euthanized during treatment with 4 of the 6 cats (66%) dying within 3 days of starting treatment. Conclusions We describe the effective use of injectable remdesivir and PO GS‐441524 for the treatment of FIP in cats. Success occurred using different treatment protocols and with different presentations of FIP including cats with ocular and neurological involvement.

Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV), manifesting as effusive (wet) or non-effusive (dry) forms. Granulomatous lesions in the gastrointestinal tract, particularly the colon, are rare and pose diagnostic and therapeutic challenges. A 7-year-old castrated male domestic shorthair cat (4.1 kg) presented with anorexia and vomiting. Blood tests showed an albumin:globulin ratio of 0.5, a mild elevation in aspartate aminotransferase, mild leukocytosis, and a severe elevation of feline serum amyloid A. The abdominal ultrasound and computed tomography imaging showed a mass in the transverse colon and surrounding mesenteric lymph nodes. The mass was observed to be relatively well vascularized, with areas of low-density uneven necrosis. Histological examination revealed severe pyogranulomatous inflammation with macrophages, neutrophils, and lymphocytes predominantly present in both the affected colon and lymphoid tissues. Immunohistochemistry for feline infectious peritonitis (FIP) virus antigen of the lesion showed a strong positive result, confirming limited and localized lesion induction by FIP virus infection. The cat received GS-441524 for 12 weeks, resulting in clinical improvement, lesion resolution, and normalized lab results. RT-PCR and antibody tests were negative post-treatment. This case report describes a rare presentation of FIP virus infection, characterized by localized lesions confined to a specific segment of the colon. In this case, treatment with the nucleoside analog GS-441524 was very effective in improving the localized lesion and demonstrated excellent efficacy in clearing the FIP virus.

Feline infectious peritonitis (FIP) historically has been a fatal disease in cats. Recent unlicensed use of antiviral medication has been shown to markedly improve survival of this infection. An 8‐month‐old female spayed domestic short‐haired cat undergoing treatment for presumptive FIP with the antiviral nucleoside analog GS‐441524 developed acute progressive azotemia. Abdominal ultrasound examination identified multifocal urolithiasis including renal, ureteral, and cystic calculi. Unilateral ureteral obstruction progressed to suspected bilateral ureteral obstruction and subcutaneous ureteral bypass (SUB) was performed along with urolith removal and submission for analysis. A 2‐year‐old male neutered domestic medium‐haired cat undergoing treatment for confirmed FIP with GS‐441524 developed dysuria (weak urine stream, urinary incontinence, and difficulty expressing the urinary bladder). This cat also was diagnosed sonographically with multifocal urolithiasis requiring temporary tube cystostomy after cystotomy and urolith removal. In both cases, initial urolith analysis showed unidentified material. Additional testing confirmed the calculi in both cats to be 98% consistent with GS‐441524. Additional clinical studies are required to determine best screening practices for cats presented for urolithiasis during treatment with GS‐441524.

Feline infectious peritonitis (FIP) is a fatal but now treatable disease in cats caused by feline coronavirus (FCoV). This study prospectively investigated viral coinfections in 100 cats diagnosed with FIP and subsequently treated with oral GS-441524 (Bova UK) and their influence on outcome, focusing on viruses potentially associated with feline chronic gingivostomatitis (FCGS). Cats were tested for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline calicivirus (FCV), feline herpesvirus (FHV), feline foamy virus (FFV), and feline gammaherpesvirus (FcaGHV1). Coinfections were identified at the following frequencies: FCV (27), FFV (22), FHV (6), FIV (4), FcaGHV1 (2), and FeLV (2, both progressive infections). FFV infection was significantly associated with FIV (pF = 0.0021) and FHV (pF = 0.0226) infection. FCGS was present in 25/97 cats with FCV infection being associated with FCGS (pF = 0.0032); no significant associa-tions were found for the other viruses and FCGS. The 42-day oral GS-441524 treatment’s success rate was 94% (five cats died, one relapsed). Coinfections did not significantly influence disease severity or treatment outcome, although the low number of cases for some pathogens warrants further investigation. However, advanced age was associated with treatment failure, potentially due to delayed diagnosis as FIP is considered to be less common in older individuals, or to age-related changes in immune function. In summary, viral coinfections, particularly with FCV, were common and should be considered in the clinical and hygienic management of cats with FIP.

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCLTM) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was <5% and <15%, respectively; and AGP was stable in serum stored for at least 8 days at room temperature, at 4 °C and at −20 °C. Cats with confirmed FIP had significantly higher serum AGP concentrations (median: 2954 µg/mL (range: 200–5861 µg/mL)) than those with other inflammatory diseases (median: 1734 µg/mL (305–3449 µg/mL)) and clinically healthy cats (median 235 µg/mL (range: 78–616 µg/mL); pKW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP (pMWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCLTM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment’s effectiveness and identify potential relapses at an early stage.

As previously demonstrated by our research group, the oral multicomponent drug Xraphconn® containing GS-441524 was effective at curing otherwise fatal feline infectious peritonitis (FIP) in 18 feline coronavirus (FCoV)-infected cats. The aims of the current study were to investigate, using samples from the same animals as in the previous study, (1) the effect of treatment on fecal viral RNA shedding; (2) the presence of spike gene mutations in different body compartments of these cats; and (3) viral RNA shedding, presence of spike gene mutations, and anti-FCoV antibody titers in samples of 12 companion cats cohabitating with the treated cats. Eleven of the eighteen treated FIP cats (61%) were shedding FCoV RNA in feces within the first three days after treatment initiation, but all of them tested negative by day 6. In one of these cats, fecal shedding reoccurred on day 83. Two cats initially negative in feces were transiently positive 1–4 weeks into the study. The remaining five cats never shed FCoV. Viral RNA loads in feces decreased with time comparable with those in blood and effusion. Specific spike gene mutations linked to systemic FCoV spread were consistently found in blood and effusion from treated FIP cats, but not in feces from treated or companion cats. A new mutation that led to a not yet described amino acid change was identified, indicating that further mutations may be involved in the development of FIP. Eight of the twelve companion cats shed FCoV in feces. All but one of the twelve companion cats had anti-FCoV antibodies. Oral treatment with GS-441524 effectively decreased viral RNA loads in feces, blood, and effusion in cats with FIP. Nonetheless, re-shedding can most likely occur if cats are re-exposed to FCoV by their companion cats.