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Maureen’s going to give me grief over the length of this post, but the use of antivirals in cats is important topic with a lot of issues to consider, so let’s dig into it once again.

Access to effective antivirals to treat feline infectious peritonitis (FIP), particularly GS-441524 (a relative of the anti-COVID-19 drug remdesivir), has been a game-changer in the truest sense in veterinary medicine: it has changed FIP from an almost invariably fatal disease to one that has a 90% or greated cure rate. It’s truly amazing how it has impacted the care of affected cats.

BUT we have decades of history in human and veterinary medicine of screwing up the use of remarkable, game-changing anti-infective drugs.

I sometimes tell students that my biggest concern with FIP now is that in 10 years, we’ll be saying that we used to have great drugs for treating FIP, and we had really high cure rates and saved countless cats, but FIP became resistant to all these drugs, so once again FIP is almost invariably fatal. That’s a bit dramatic, and I don’t think we’ll get there (I really hope not!), but it’s not unreasonable to be concerned about resistance, as more cats would end up dying from this infection.

Drugs like GS-441524 (and remdesivir) as well as molnupiravir (and its relative EIDD-1931) need to be managed as highest-tier anti-infectives, in the same way we need to manage highest-tier antibiotics. We need to avoid squandering them, so we have to use them carefully and appropriately.

There is lots of additional discussion about FIP and these new treatment options in previous blog posts, so I won’t rehash everthing again, but here’s a quick reminder of some key points:

  • FIP is caused by a very common cat visus, feline coronavirus (FCoV).
  • FCoV is carried in the intestinal tract; infection rates are high in some cat populations, but most of the time it does not cause any significant illness.
  • Some cats can shed FCoV in their feces for prolonged periods of time.
  • FIP occurs when FCoV mutates within a cat into a strain that can cause disease.

My main concern is development of antiviral resistance in the normal intestinal FCoV that is widespread in cats, because it’s common, transmissible and the origin of FIP. If we brew resistance in some cats and it gets transmitted through the population via resistant FCoV, we would end up with antiviral resistant FIP, which could kill a lot of cats.

Anytime we use an antiviral, there’s some chance for resistance to emerge. It’s a race between the drug killing the virus and the virus randomly mutating in a way that makes it resistant to the drug. Usually, the drug wins and the virus is eliminated, but sometimes, it doesn’t. If a resistant strain of the virus emerges, and the cat potentially spreads that virus to another cat, and then it spreads to another cat, and then another and another… and the more cats that are carrying the resistant strain, the faster it spreads.

The more we use antivirals, the more risk of resistance emerging, and spreading.

When we treat cats with FIP, the risk of resistance emerging in the virus is low. If the virus in an individual cat becomes resistant, it’s not a huge issue beyond the individual because after the FCoV mutates to to the FIP form, it’s not typically shed in the feces, so the risk of transmission to other cats is limited. The bigger risk is if the cat has a concurrent intestinal infection with “regular” FCoV that becomes resistant, since the FCoV form is much more transmissible and some cats will shed the virus for prolonged periods of time. We accept this risk when we treat cats with FIP, because the risks are hopefully low and the rewards (saving the cat’s life) are very high.

However, when we use these critical drugs in other situations, that risk/reward ratio can be very different. The two main scenarios of concern for me at this point are:

1. Treatment of enteric feline coronavirus

    Intestinal infection in cats with FCoV is common, but it doesn’t cause disease in most cases, and when it does, it’s usually mild disease in kittens. Antivirals will likely have an impact on intestinal infections, and there are data showing GS-441524 will reduce FCoV shedding in cats. But intestinal FCoV infection isn’t much of health risk. With lots of FCoV in the intestine, where antiviral levels may not get as high as they need to to kill the virus effectively, and the risk of long-term shedding of the virus, the risks of resistance emerging AND spreading to other cats are concerning. Treating cats with mild intestinal infections doesn’t provide much benefit, but it could create a lot of risk regarding these critical drugs.

    2. Treatment of other diseases

    This is something that’s becoming a major concern. GS-441524 and EIDD-1931 are approached by some as “miracle” drugs. And they are miracle drugs – for FIP. That does NOT mean they will work well for other conditions, or work well enough to justify the risk. There’s been a lot of talk lately about antiviral treatment of cats with feline chronic gingivostomatitis (FCGS). It’s a nasty disease (often requiring extraction of all the teeth in the mouth), so I can understand the desire to try just about anything, but there’s not much evidence yet that either of these drugs will help.

    A lot of the discussion about treatment of FCGS with these antivirals revolves around a research abstract that was presented at the 2025 ACVIM Forum (Colon et al.). The researchers looked at 8 cats with FCGS. All the cats were negative for feline leukemia virus and feline immunodeficiency virus. Five were treated with molnupiravir and three were “untreated” (it’s not clear if these three got other “standard” treatments, but they did not get antivirals). By week 4, four of the five treated cats had improved lesion scores (it’s important to know the degree of improvement to put the response into context, but unfortunately abstracts have limited space so this detail was not provided). Decreased (note that they did not say “elimination of”) FVoC shedding was also noted in two of these five cats. There was no change in the 3 control cats.

    What does this tell us?

    • It doesn’t tell us molnupiravir is effective for treating FCSG.
    • It doesn’t tell us that molnupiravir is superior to standard approaches for treating FCSG.
    • It doesn’t tell us the benefits of molnupiravir treatment in these cats outweigh any risks.
    • It does tell us that a proper clinical trial would likely be worth doing to see if this drug really is effective compared to standard approaches, and to investigate potential risks (e.g. emergence of resistance, adverse effects in the cats, human exposure risk). As the authors said “Further research is needed to confirm [molnupiravir’s] efficacy and broader applications in cats with FCV.”

    Unfortunately, this abstract has been jumped on as evidence that molnupiravir works to treat FCGS. People want another treatment option for this awful disease. Some are also looking for a cheaper treatment option than expensive dental extractions (I understand that too, especially when it comes shelters and rescues). But, we need to consider the big picture:

    • A cat with FCGS may also have a concurrent intestinal infection with FCoV. Given the high shedding rates in cats, it’s a very realistic concern. While it’s possible antivirals might help with some cases of FCGS, the abstract only tells us someone needs to do a much more thorough study on this. Such a study would need to include testing treated cats for concurrent FCoV infection before and after treatment, and looking for resistance mutations in the virus.
    • I also really don’t want to see these drugs used in lieu of full mouth dental extractions when that is clearly needed. It’s just like I wouldn’t use meropenem (a highest-tier antibiotic) in an animal if there was a definitive (or at least critically important) concurrent treatment that wasn’t being done (like removing an infected implant). 

    Another important consideration is the potential impact of this use on access to these lifesaving drugs for FIP. This is mainly a concern in the US, where these drugs are currently accessible, but not licensed for use in cats. The US FDA has allowed them to be used based on the benefits for treatment of FIP outweighing the potential risks of allowing use of an unlicensed drug. The more we deviate from what they based their decision on (use for treatment of FIP), the greater the risk that they will change their permissive stance, and we could lose access to these drugs altogether. Losing access to these antivirals for FIP would be devastating, and it’s not implausible. The FDA’s risk assessment for use in cats with FCGS could be very different, since it’s a non-fatal disease that has other established treatment approaches (even though it’s still nasty and treatment isn’t easy). One pharmacy in the US is now selling a molnupiravir product specifically marketed for FCSG (and it also contains doxycycline (an antibiotic) which just adds more “ugh!” to the picture). That’s just asking (not in a good way) for FDA intervention. The pharmacy has a notice on their website saying the product is meant for stomatitis associated with calicivirus, but few people read notices at the bottom of the page, many people won’t care about that, nor that there’s no evidence that molnupiravir is effective against feline calicivirus. I assume they’re trying to build in a viral infection justification for a new product, versus a product based on evidence of efficacy and need.

    Let’s not repeat decades of failures with how we handle antimicrobials by taking chances on how we use these critical antivirals for cats. I’m fine with exploring their use for other conditions, but before we start risking the efficacy of or access to these miraculous FIP treatments (which saves the lives of countless cats), we need to have solid evidence of efficacy for other uses AND risk : benefit analysis that points convincingly toward “benefit.”