Feline Infectious Peritonitis: A Promising Human Antiviral Treatment for Feline Infectious Peritonitis in Cats

The emergence of exotic diseases in humans, such as the Ebola virus and SARS, has intensified research into the replication of human RNA viruses and the development of new antiviral treatments. This research is now benefiting veterinary medicine. For example, feline infectious peritonitis (FIP), a disease similar to a human viral infection, is benefiting from the development of a promising antiviral treatment for humans (Remdesivir, GS-5734). Veterinary researchers have successfully tested the safety and efficacy of a closely related nucleoside analog, GS-441524, in cats with feline infectious peritonitis.

Feline infectious peritonitis, a contagious viral disease that primarily affects kittens, is almost always fatal. It is estimated to kill up to 1.4% of affected cats worldwide. The coronavirus involved, an RNA virus, is transmitted via the fecal-oral route and is particularly difficult to control and diagnose. Present in virtually all cat populations (catteries, shelters, breeding facilities), it is shed by more than 60% of cats living in groups. In the absence of an effective vaccine, the only therapeutic hope lies in antiviral drugs.

GS-5734, a small-molecule antiviral drug that targets specific proteins involved in RNA virus replication, is one of the most promising treatments against emerging viruses in humans. Studies have demonstrated its effectiveness in preventing Ebola virus infection in rhesus monkeys and in inhibiting coronaviruses in both tissue culture and mouse infection models.

These results have attracted the attention of veterinary researchers in the United States, led by Professor Niels C. Pedersen (University of California, Davis), who has been studying the complex nature of feline infectious peritonitis (FIP) for over fifty years. In an initial study inducing experimental feline infectious peritonitis (FIP), the team demonstrated that GS-5734 and its nucleoside analog, GS-441524, were comparably effective against feline infection. Additional tests with GS-441524 alone—a chemically simpler compound—were conducted in laboratory cats. The results, which demonstrated high efficacy of GS-441524 against experimentally induced feline infectious peritonitis (FIP), paved the way for a field clinical trial in cats naturally infected with FIP.

Of the 31 cats included in the study, 26 completed the treatment, which lasted a minimum of 12 weeks, and 5 died or were euthanized due to complications. The clinical response in these 26 cats was remarkable: fever subsided within 12 to 36 hours, accompanied by a marked improvement in appetite and activity level, as well as significant weight gain (ranging from 20 to 120 percent based on measurements taken during and after treatment). Similarly, in these 26 cats with the most common form of feline infectious peritonitis, known as the “wet” form, abdominal effusions rapidly resolved, as early as 10 to 14 days after the start of the treatment regimen.

Of the 26 treated cats, 18 required no additional treatment. However, 8 other cats experienced a recurrence of the disease within 3 to 84 days (average 23 days), but they all responded well to a higher dosage. In total, 25 of the 26 treated cats achieved sustained remission from feline infectious peritonitis, although one subsequently died from a congenital heart defect unrelated to the disease.

Encouragingly and somewhat unexpectedly, cats with dry feline infectious peritonitis (FIP) and older cats also responded well to treatment with GS-441524, just as cats with exudative FIP and kittens did. The safety profile of GS-441524 is also impressive. No systemic signs of toxicity were observed over the entire treatment period, which ranged from 12 to 30 weeks.

Until recently, the prognosis for cats with feline infectious peritonitis (FIP) was virtually zero, as no treatment had proven effective. Cats that developed the disease inevitably died within a few days, weeks, or months. Today, researchers are significantly more optimistic. Two safe and effective antiviral drugs have proven their worth, even exceeding expectations, and demonstrate that feline infectious peritonitis, regardless of the form of the disease, can be treated with nucleoside analogs.

In fact, GS-441524 is the second targeted antiviral drug, after GC376, to be evaluated for the treatment of cats with feline infectious peritonitis over the past three years. These two drugs inhibit viral replication in two very different ways. Although their results are virtually identical, GS-441524 appeared to be more effective. To date, 6 of the 20 cats treated with GC376 remain in remission, compared with 25 of the 31 cats treated with GS-441524.

Thanks to these trials, we now know that small molecules targeting specific stages of RNA virus replication are capable of curing feline infectious peritonitis. However, the results obtained cannot be immediately translated into commercially available drugs, much to the despair of owners of cats with feline infectious peritonitis. Although these advances are promising, there is still much to learn about feline infectious peritonitis.