Complete clinical study: Zuzzi-Krebitz AM, Buchta K, Bergmann M, Krentz D, Zwicklbauer K, Dorsch R, Wess G, Fischer A, Matiasek K, Hönl A, Fiedler S, Kolberg L, Hofmann-Lehmann R, Meli ML, Spiri AM, Helfer-Hungerbuehler AK, Felten S, Zablotski Y, Alberer M, Both UV, Hartmann K. Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion-A Prospective Randomized Controlled Study.Viruses. 2024 Jul 16;16(7):1144. doi: 10.3390/v16071144. PMID: 39066306; PMCID: PMC11281457.
The discovery of GS-441524 as an effective antiviral drug for cats with feline infectious peritonitis (FIP) has enabled feline patients to survive this once incurable, fatal disease. In the UK and Australia, GS-411524 is already legally available, while in the US the drug has only recently been available through selected compounding pharmacies. An 84-day treatment cycle has been shown to be successful in various clinical studies and has become an unofficial standard protocol. From a practical point of view, the daily administration of the drug for 12 weeks, as well as the cost of such treatment, can make it difficult or even impossible for cat owners to complete the entire prescribed treatment.
The aim of the researchers in Germany and Switzerland was to evaluate whether a 42-day treatment with GS-441524 is as effective as the currently recommended 84-day protocol. In a prospective randomized controlled treatment study, 40 cats were randomized to receive 15 mg/kg GS-441524 orally once daily for 42 or 84 days. Patients were diagnosed with FIP based on either FCoV RNA detected by RT-qPCR or RT-PCR in effusion in at least one body cavity with altered laboratory parameters typical of FIP. In addition to the diagnosis of FIP, other inclusion criteria included the presence of abdominal and/or pleural effusion, negative FeLV and FIV status, a body weight of at least 2 kg, and the absence of other serious diseases. The age of the cats ranged from 5.1 to 116.3 months, with 17 of the 40 cats being less than 1 year old. Breed distribution was as follows: 40 % Domestic Shorthairs (DSH), 20 % British Shorthairs (BSH) and 40 % other breeds. At the start of the study, 63 % cats had abdominal effusion, 12 % pleural effusion, and 25 % effusion in both cavities.
Each patient was treated for the first 7 days at the Center for Clinical Veterinary Medicine at the LMU in Munich. Treatment groups were blinded until day 7 of the study. The cats remained in their owners' homes for the remaining days of the study and returned every 2 weeks for follow-up examinations and diagnostic tests at the clinic. Tests included abdominal and thoracic ultrasonography, blood chemistry, hematology, urinalysis, measurement of viral RNA in effusion, blood, and feces, and anti-FCoV antibodies. Detailed cardiological and neurological examinations were performed at study entry. The final re-examination was performed 168 days after the start of treatment.
GS-441524 was supplied as 50mg tablets and was legally imported from the UK. Owners kept diaries documenting items such as activity, stool consistency, food intake and body weight. 19 cats (of 20) in each treatment group completed treatment. Two cats were euthanized during treatment (days 3 and 31) due to secondary complications.
Clinical remission was observed between days 14 and 84 with a median of 28 days, and within the first 42 days 37/40 cats went into complete clinical remission. Every cat that completed treatment showed significant improvement in hematological and clinical chemistry parameters. At the beginning of the study, viral RNA was detected in the blood of 35/40 cats, and by day 28 no more viremia was noted in any cat. During the second phase (days 42 to 84) of the study, in which only the long-term treatment group received the drugs, no significant differences were found in viral load in blood, effusion and feces or anti-FCOV antibodies. By 168 days, all 38 cats remaining in the study were in complete remission. Two cats with neurological or ocular signs also fully recovered during treatment.
The most frequently observed adverse events were diarrhea in 25/40 cats (20 % of which were diagnosed as severe based on stool evaluation), elevation of liver enzymes (mild to moderate) in 24/40 cats between days 1 and 84, lymphocytosis in 27/40 cats and a slight increase in SDMA above the reference interval in 25/40 cats. None of the patients experienced adverse effects related to the administration of GS-441524.
This study demonstrated that a shorter treatment of 42 days with oral GS-441524 was as effective as the currently recommended 84-day treatment. GS-441524 was generally well tolerated, with no significant adverse reactions noted. Limitations include that all patients received continuous professional veterinary care during the first 7 days of treatment, which is not common in most clinical practice. In addition, only patients with wet FIP were included and only the oral form of GS-441524 was used. The preparation used in the study was legally manufactured in a strictly controlled manner by BOVA Specials in London, UK. Many cat owners around the world still purchase oral and/or injectable GS-441524 from "black market" sources, so it is unknown whether the 42-day treatment is equally effective in these patients. -BJP
More details:
Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, Liu H. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis.J Feline Med Surg. 2019 Apr;21(4):271-281. doi: 10.1177/1098612X19825701. Epub 2019 Feb 13. PMID: 30755068; PMCID: PMC6435921.
Murphy BG, Perron M, Murakami E, Bauer K, Park Y, Eckstrand C, Liepnieks M, Pedersen NC. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies.Vet Microbiol. 2018 Jun; 219:226-233.doi: 10.1016/j.vetmic.2018.04.026. Epub 2018 Apr 22. PMID: 29778200; PMCID: PMC7117434.
We thank Richard Malik and Sally Coggins for their advice and assistance in the preparation of this paper.
FIP treatment protocols - what's new?
Antivirals currently legally available in the UK and other countries through importation include remdesivir (injection), GS-441524 (oral suspension and oral tablets) and EIDD-1931 (oral tablets). The following recommendations are based on published and unpublished data and experience. The treatment of individual cases remains within the competence of the attending veterinarian. The dosage below is based on experience with the use of reputable preparations with known antiviral content. The extrapolation does not apply to other oral preparations for which the active ingredient and/or its content is unknown or not provided by the manufacturer.
Use of oral GS-441524 throughout treatment, including initiation of treatment
Oral GS-441524 (available as a 50 mg/ml suspension and 50 mg tablets) can be used from the start of FIP treatment for a full (eg, 12-week/84-day) cycle. It is important to support owners in their cats' medication, which can be difficult. GS-441524 oral suspension or tablets can be given with a small treat (tablets can be crushed for this) or directly into the cat's mouth. Further study is needed to examine the effect of food on absorption, but it is recommended that it be given in a small treat or on an empty stomach, with an hour or more gap before a larger meal.
Fasting cats at night can increase their hunger to facilitate the administration of the medicine in the morning, and similarly for the evening dose. However, starving kittens is never recommended as they will not be able to handle it. Any withholding of food must be adapted to the cat's age.
Injectable remdesivir is intended for cats that cannot be treated orally
Injectable remdesivir (10 mg/ml) is effective in the treatment of FIP but is associated with some side effects (see below), particularly pain on subcutaneous injection occurring in 50 % cats. Previous FIP treatment protocols suggested that this drug be used initially before switching to oral GS-441254. However, we now know that cats with FIP can be successfully treated with oral GS-441524 from the first day of treatment. This avoids injection pain and reduces treatment costs (the dose per cat weight using GS-441524 is cheaper than remdesivir). The use of injectable remdesivir should be reserved for the following situations:
Severe neurological symptoms and inability to swallow or tolerate oral medications;
Extremely dehydrated/unruly cats;
Cats that cannot be treated orally for other reasons.
In certain circumstances, if the cat is hospitalized and has decreased appetite, which affects the ability to administer medication, 48 hours of remdesivir (given intravenously, not subcutaneously) may result in significant clinical improvement that may facilitate subsequent oral treatment with GS-441524. The rest of the treatment cycle can then be administered in the form of oral GS-441524.
The switch between remdesivir and oral GS-441524 can be immediate, ie from one treatment to the other.
The current recommendation is to treat for at least 84 days. Some cats have been successfully treated with shorter courses, but large-scale case studies have not yet been published. If cost constraints require a shorter duration of treatment, the dose used should not be reduced and treatment should last as long as possible.
What dosage of GS-441524 and remdesivir should I use to treat FIP?
With experience and as yet unpublished data on therapeutic drug level monitoring (TDM), dosing recommendations have increased over previous FIP treatment protocols. However, evidence shows that more than 85 % cats respond to previously recommended drug dosing, which is still a high rate. However, based on TDM studies, we now know that individual cats vary in their absorption of oral GS-441524, with those that absorb it poorly requiring higher doses to achieve clinical and biochemical remission. Ideally, dosage should be adjusted based on TDM, if available (see below), or based on response to treatment.
Compared to previous FIP treatment protocols, the following changes in dosing recommendations are important:
GS-441524 is administered orally in divided doses twice daily (every 12 hours) to optimize serum levels of GS-441524;
Higher dosages may overcome malabsorption problems in some cats and have a better chance of crossing the blood-brain barrier and the blood-ocular barrier;
Dosage should be adjusted according to response and TDM if available.
Clinical presentation
GS-441524 PO dosing
Remdesivir IV or SC injection
Effusion present No ocular or neurological symptoms
6-7.5 mg/kg q 12h ie 12-15 mg/kg divided into 2 doses per day
10 mg/kg q 24h
Absence of effusion No ocular or neurological symptoms
6-7.5 mg/kg q 12h
12 mg/kg q 24h
Ocular symptoms
7.5-10 mg/kg q 12h
15 mg/kg q 24h
Neurological symptoms
10 mg/kg q 12h
20 mg/kg q 24h
PO, per os – orally; IV-intravenous; SC – subcutaneously; q – every x hours
Cats should be re-examined after 1-2 weeks (sooner if not improving or worsening) and dosage adjusted depending on monitoring at this point.
NOTE ON WEIGHING CATS: During treatment, it is very important to weigh the cats once a week, using accurate scales, e.g. on cat or baby scales. With successful treatment, the kittens will gain weight and/or grow, necessitating an increase in the dose to ensure that the dose of antiviral given is still adequate for the type of FIP being treated according to Table 1. Failure to increase the dose as the kitten grows appears to be one of the most common causes poor response to treatment and treatment failure.
What should I do if FIP relapses?
e.g. recurrence or insufficient resolution of effusion, pyrexia, development of new ocular or neurological symptoms, or persistent clinicopathological abnormalities:
Make sure you are still sure the cat has FIP; reassess the diagnosis, seek further pathology and consider repeat sampling (eg, external laboratory analysis and culture of any fluid; cytology or lymph node biopsy ± detection of feline coronavirus antigen or RNA, but remember that with treatment the virus is more difficult to find), AGP;
Consider TDM, if available, to monitor GS-441524 serum levels to inform dosing;
If relapse occurs during treatment, increase the dose of GS-441524 (or remdesivir) by 2-3 mg/kg per dose and monitor as above, ensuring that treatment is not stopped before the cat is in normal clinical condition and based on clinical pathology results for at least 2 weeks. Dosage increases depend on the dosage the cat is receiving at the time of relapse, the nature of the relapse and financial resources, but can be up to the recommended dosage for neurological FIP (see dosage chart above) or even higher (seek advice when considering this option );
If relapse occurs after stopping treatment, restart GS-441524 (or remdesivir) at a higher dose (at least 2-3 mg/kg higher than previously used) and ideally continue treatment for an additional 12 weeks. The increased dosage used will depend on the dosage the cat was receiving prior to the relapse and the nature of the relapse, but may be up to the dosage recommended for neurological FIP;
If the cat is already on a high dose of GS-441524 and/or serum TDM levels are adequate, consider switching to EIDD-1931 (see below) and seek advice (email advice for FIP or specialists) as adjunctive therapy such as mefloquine feline interferon or a polyprenyl immunostimulant may be an option (see below).
Treatment with EIDD-1931
This drug is another antiviral effective in the treatment of FIP in cats, although there is much less evidence of its use than GS-441524. The recommended dosage is 15 mg/kg every 12 hours and is available as 60 mg tablets for oral use. Potential adverse effects include cytopenia, especially neutropenia, rarely pancytopenia, decreased appetite/nausea, increased ALT enzyme activity, and potential renal compromise. The use of EIDD-1931 should be reserved for:
cats that do not respond to treatment with GS441524 or remdesivir despite adequate dosing (ideally assessed by TDM);
cats that relapse after treatment with GS-441524 or remdesivir at an appropriate dose.
Treatment with feline interferon (IFN), polyprenyl immunostimulant or mefloquine
In some cats, combinations of IFN omega, the immunostimulant polyprenyl, and mefloquine were used in the post-treatment period with GS-441524 (or remdesivir); however, there is currently no evidence to suggest that they are necessary, as even without this adjunctive treatment, a high success rate of over 85 % has been reported;
Mefloquine is also used to treat cats with FIP when financial constraints make it absolutely impossible to use a full course or increased dosage of more potent antivirals such as GS-441524. Studies are needed to evaluate its effectiveness, but it should only be used when absolutely no alternatives are available, as GS-441524 is known for its high potency.
A cat with Feline Infectious Peritonitis (FIP) in Cyprus shows several signs of the disease, including a swollen abdomen due to fluid build-up in the abdominal lining, unkempt fur and poor muscle condition.
The first signs of problems appeared at the end of last year (2022) in Cyprus, an island state in the eastern Mediterranean, known for its abundance of free-roaming cats. Some veterinarians there have begun to see an increase in cases of Feline Infectious Peritonitis (FIP), a fatal disease of cats.
The cats had a fever, were lethargic, losing weight and did not want to eat. Some had swollen abdomens, others had tumor-like lesions. Some were staggering, uncoordinated. Some had inflamed, cloudy or discolored eyes.
FIP usually occurs in cats as a rare reaction to infection with a common pathogen, feline enteric coronavirus (FECV). The virus is shed in the feces of infected cats, from where it can be spread to other cats. FECV is a subtype of feline coronavirus (FCoV), which is one of hundreds of known coronaviruses and does not infect humans. However, this virus is very common among stray cats and cats that live with several other cats. Cats infected with FECV are generally asymptomatic and remain healthy. However, sometimes the virus mutates and causes FIP.
In Cyprus, thousands of cats were diagnosed in the first months of this year. The disease spread rapidly, contradicting common ideas about how FIP develops.
"It's just not right," said Dr. Danielle Gunn-Moore when she discovered this summer that the number of diagnoses on the island had increased 40-fold compared to the previous year. Gunn-Moore is Professor of Feline Medicine at the Royal (Dick) School of Veterinary Studies at the University of Edinburgh.
So far unpublished work, which was published on the bioRxiv portal in November before being published in a peer-reviewed journal, offers preliminary answers to the question of why so many cats fell ill in Cyprus. Based on RNA sequencing of samples from dozens of cats with FIP, the authors of the paper argue that a strain of coronavirus that arose from separate feline and canine coronaviruses may have combined, linking the fecal excretion and infectivity of the common FECV virus with the virulence of the mutated FIP virus to one pathogen.
"In normal FIP, the FIP virus is rarely spread," said Gunn-Moore, the paper's author. "That's a huge difference in the case of a new epidemic. Everything says that it is directly portable.”
Veterinary researchers contacted by the VIN news service for comment on the paper called the evidence "interesting" and "highly suggestive" but not definitive. They say that more research is needed, which the authors say is in full swing.
Concerns are growing on the "cat island".
In short
Thousands of cats on the Mediterranean island of Cyprus have been diagnosed this year with feline infectious peritonitis, a fatal and usually rare feline disease.
The disease spread quickly among the many free-ranging cats on the island, upsetting the conventional wisdom about how FIP develops.
The authors of the new paper, which has not yet been peer-reviewed, say the outbreak was caused by a new strain of the pathogen that evolved from separate cat and dog coronaviruses, a recombination that increases its ability to spread.
Veterinarians in Cyprus are treating many sick cats with antivirals, some of which have been developed to treat humans with Covid-19.
A cat imported to the UK from Cyprus in August has been confirmed to be infected with the new strain.
dr. Demetris Epaminondas, vice-president of the Pancyprian Veterinary Association (PVA), first learned of the "worryingly increased number of FIP cases" last December from his wife, a clinical veterinarian. He soon began receiving similar messages from other doctors.
A possible increase in the deadly feline disease is causing particular concern in the area, sometimes called "cat island," where cats roam, stretch, hunt and sleep everywhere. Large colonies of cats, which are revered as saints, live in and near monasteries, where they are cared for by monks. Elsewhere, residents feed and care for neighborhood felines. The number of cats on the island is not officially estimated.
PVA sent a questionnaire to 150 veterinary clinics in Cyprus to try to find out what was going on. Twenty-four clinics reported a total of approximately 500 cases of FIP in the first three months of 2023, a tenfold increase over the first three months of the previous year. In April, the number of reports peaked at around 2,000 cases.
These numbers only include cats on about half the island, an area of more than 2,000 square miles. Cyprus has been divided since the 1970s: The area to the south and west is under the control of the Republic of Cyprus, which has a Greek Cypriot majority and is a member of the European Union. The area to the north is occupied by Turkish military forces and is not under the effective control of the Cypriot government. There have been no official FIP announcements from the north.
dr. Charalampos Attipa, a veterinary pathologist from Cyprus, noticed the increase in cases in January while reviewing test results for Vet Dia Gnosis Ltd., a veterinary diagnostic laboratory he helped found in 2021.
There is no single test that can diagnose every case of FIP. Therefore, the diagnosis is often made based on a summary of clues from the patient's history, physical examination, and various diagnostic tests, including PCR tests. PCR stands for polymerase chain reaction, a technique that allows users to rapidly amplify a small sample of genetic material for study.
In the diagnosis of FIP, small segments of the genetic material of the coronavirus are identified by PCR in a sample of fluid from the lining of the abdomen (peritoneum) or lungs (pleura) or from the spine, or from a biopsy of tumor-like lesions.
In 2021 and 2022, Vet Dia Gnosis recorded three and four positive PCR tests in cats with FIP in Cyprus. From January to August 2023, 165 positive FIP-related PCR tests were recorded.
"These are only cats whose owner paid for the PCR to be performed," said Attipa. "It is most likely the tip of the iceberg. But we don't really know the size of the glacier. That's the problem."
Attipa, who started at the University of Edinburgh in April, is the lead author of the preprint paper. He is also a key member of an international collaboration investigating the virology, epidemiology and therapy of the current epidemic.
At the beginning of the year, Attipa, Epaminondas and others focused on raising awareness among veterinarians and the public. The effort led to several missteps, including a report picked up by multiple news outlets that 300,000 cats had died from the disease. Epaminondas said the figure was an unofficial and inaccurate estimate by animal welfare organizations. Additionally, the PVA estimate of 8,000 infected cats by mid-July was incorrectly reported by the Associated Press as 8,000 dead. There is no official estimate of the number of dead.
The number of PCR-confirmed cases began to decline in April, but this may not be cause for celebration just yet.
"At first, people didn't know what the disease was, so they took the animals to the vet for a diagnosis," Epaminondas said. However, with increasing awareness, cat owners and carers have been aware of an increase in FIP and clinical signs such as a swollen abdomen present in one form of the disease. "Because they can find treatment on the black market, they don't want to spend money to properly diagnose the disease," he said.
In recent years, antiviral compounds have shown remarkable promise in reversing the course of FIP. However, these compounds are not approved for veterinary use in many countries. As a result, a black market for antiviral drugs, mostly made in China, is flourishing, fueled by desperate cat owners who treat their animals on their own. A 2021 study of cats given unlicensed antivirals in the US found a survival rate of 80 % and above.
The number of PCR tests increased again in August, which may be due to the Cypriot government approving the veterinary use of molnupiravir, an antiviral drug used to treat Covid-19 in humans. Cats must be PCR positive for their owners or caretakers to receive a prescription.
According to Epaminondas, caseload data for most of the second half of the year, based on clinic surveys, should be available soon.
dr. J. Scott Weese, an infectious disease veterinarian at the Ontario Veterinary College at the University of Guelph, said in an email to VIN News that the epidemiology of the outbreak is not well described, adding that it is "a common problem in field studies where the information is piecemeal and often unofficial".
According to Weese, the number of cases confirmed by PCR - 165 - is very small, especially for a country with a lot of feral cats. He also said that the rate of diagnosis based on questionnaires begs the question: Are more diagnoses due to a significant increase in the disease, a significant increase in testing, or both?
“There appears to be an increase in the incidence of FIP in Cyprus. It's hard to say by how much," he said. "When there is more discussion and awareness increases, there are also more diagnoses of an endemic disease that may have been there all along, but was just ignored. Often times these are combined situations where there is a real increase or a small local clustering, but the increased discussion and testing leads to an overestimation of the rate of change.”
He added: “I am not ruling out that this was a real epidemic or that this is a worrying new strain. We just don't know (or at least I don't). This work shows that we need to deal more with this issue."
Introducing FCoV-23
Basic information of FIP
If you find the specifics of feline infectious peritonitis difficult to understand, ask Dr. Brian Murphy for advice: It is. "FIP is probably the most complicated virus in veterinary medicine," said Murphy, a veterinary pathologist and FIP researcher at the University of California, Davis, School of Veterinary Medicine. Much of what science knows about FIP was pioneered by Murphy's mentor, Dr. Niels Pedersen, who is already retired.
FIP is caused by mutations in a ubiquitous and otherwise insignificant pathogen called feline enteric coronavirus. These mutations allow the virus to infect immune system cells called macrophages, which multiply and cause deadly inflammation. FIP is estimated to affect 1.3 % cats, most often kittens in catteries and shelters.
There are two forms of FIP: wet and dry. Cats may initially have one form and later develop another. In wet FIP, the fluid created as a result of inflammation accumulates most often in the abdomen, less often in other parts of the body. In dry FIP, the patient develops tumor-like lesions in the abdomen, chest, eyes, and/or brain. Early symptoms of FIP include fever, loss of appetite, weight loss, and depression. Cats with neurological FIP may develop lack of coordination, seizures, and dementia. Eye disease can cause inflammation, discoloration, or clouding of a cat's eyes, which impairs vision.
No test can diagnose every case of FIP with absolute sensitivity and specificity. Therefore, the diagnosis is often established based on a summary of clues from the patient's history, physical examination, and various diagnostic tests.
First identified in the 1950s, FIP was considered a death sentence for decades. However, in recent years, antivirals – including those used against the coronavirus that causes Covid-19 in humans, such as remdesivir, molnupiravir and Paxlovid – have been shown to reverse the course of FIP in cats. None of these antivirals are approved for veterinary use in the United States (except at universities that are researching these drugs in cats with FIP). These medicines are variously available for veterinary use in several European countries, including Cyprus, Finland, Norway, Sweden and the United Kingdom, as well as Australia and New Zealand.
In countries where the treatment is not approved by regulators, pet owners have resorted to buying unlicensed antivirals, mostly made in China, to treat sick cats themselves.
Understanding why the new strain behaves differently from what some researchers call "traditional FIP" requires a closer look at how FECV leads to FIP.
For reasons that are not fully understood, sometimes the FECV mutates inside the cat. These changes allow it to escape from intestinal cells and infect a key cell of the immune system, the macrophage. This macrophage-infecting virus is known as the FIP virus or FIPV. Now it can travel throughout the body and, in Gunn-Moore's words, "devastate the environment" and cause potentially fatal inflammation.
Once established, the FIPV coronavirus has two important characteristics: First, it is no longer an enteric virus, so it can only very rarely return to the gut to be excreted as FIPV in the feces. Second, FIPV has a gene sequence that is unique to a given cat.
FCoV-23, as the new strain has been named, appears to violate both of these schemes. Gunn-Moore said it thrives in the intestines of Cypriot cats. Furthermore, based on RNA sequencing from PCR samples, the virus in many cats had the same genetic sequence. The genetic sequencing was carried out by researchers at the Roslin Institute, an animal science research center at the University of Edinburgh.
Gunn-Moore had some early hypotheses about what might have caused the outbreak, but genetic analysis points to her main theory — that a pantropical canine coronavirus combined with a feline enteric coronavirus. Pantropic viruses can spread to different tissues in the body, a property that would allow FCoV-23 to enter other organs and nerves, as well as continue to multiply in the intestinal tract.
"I think a dog came to Cyprus and defecated on the floor. A cat that already had FECV then got dog feces on her feet, licked her paws, and got both viruses," she said. ” And this is what these viruses do, they recombine, they are party animals. They get together and go, 'Hey, do you want some of this? Shall I give you some?' "
Gunn-Moore added that further work is planned to confirm the case for their direct transmission.
"We are currently carrying out experiments to sequence the virus from feces, because we need to sequence the virus and prove that it is the same sequence as in the blood," she explained.
dr. Brian Murphy, a veterinary pathologist and FIP researcher at the University of California, Davis, School of Veterinary Medicine, said the recombinant feline and canine coronavirus described in the Cyprus paper had been identified before, including by a team at Washington State University's School of Veterinary Medicine. Medicine in the 1970s.
"This is a replication of that virus, but it's a highly virulent form of the virus," Murphy said based on the evidence so far. He welcomes the scientists' plans for further genetic analysis and suggests further investigation.
"Sequencing an enteric corona or a virus coming from the gut alone is conclusive, but it's not proof," he said. "It wouldn't be a bad experiment to take fecal material containing the virus from the gut, infect cats with it, and then, when they get sick, save those cats with antiviral treatment. That would be good evidence of transmission of a virulent form of the virus.”
Murphy admitted that this kind of test on companion animals is essentially banned in Europe and would likely be very controversial. "I think most people will probably disagree with me," he said. "However, I think it can be done ethically because we have high-quality, highly effective drugs."
Dr. Maria Lyraki, an internal medicine specialist in Athens, Greece, who coordinates treatment protocols with veterinarians in Cyprus and is an author of the paper, said Murphy is right that the experiment would be proof, although some of the infected cats may not get sick if they develop an adequate immune response.
"However, it is something that we would not be able to implement from an ethical point of view," she said.
Thousands of sick cats
If the Cypriot epidemic had occurred 10 years ago, countless cats would probably have died because until recently there was no known way to stop the disease.
Antivirals have changed this situation.
Two promising products are remdesivir, made by pharmaceutical company Gilead to treat Covid-19 in humans, and the related compound GS-441524. GS, as it's called for short, was shown to be effective in reversing FIP in cats in an infectious disease study at the University of California, Davis in 2018.
Gilead has not granted a license to develop GS-441524 as a veterinary medicinal product. Remdesivir is not approved as a veterinary medicine in the United States, Canada, and some European countries.
However, since August, Cypriot vets have been able to import compounded versions of GS and remdesivir, manufactured by Bova, a veterinary pharmaceutical company based in the UK and Australia, under a special permit, to based on instructions UK Veterinary Medicines Directorate.
GS and remdesivir "are the first-line drugs we use because we have the most literature on them," Lyraki said. "But they're really expensive... which is really challenging, especially for such a large number of stray cats."
According to Epaminondas, treating one cat with these drugs can cost from €3,000 to €7,000 ($3,250 to $7,580).
"We contacted people from all over the world who are treating cases of FIP," Lyraki said. "And the specialists advised us that they use molnupiravir. There is a published literature on this drug and we have a lot of anecdotal discussion among FIP specialists around the world that it is really effective.”
The government's decision to allow veterinary use of molnupivirus has made a huge difference.
"It actually works pretty well," Lyraki said. Initially, boxes of molnupiravir were donated to the PVA to fight the epidemic. They were available at an exceptionally low price of around €100 ($108) per cat, a significant saving. The actual price of the drug is much higher, but still significantly cheaper than GS.
However, the replacement of molnupivir will not last long. Merck Sharp and Dohme BV, which sells the antiviral under the name Lagevrio, will stop making it for Europe next year after the European Medicines Agency decided earlier this year not to support the registration of molnupiravir based on its finding that the antiviral's benefit in treating Covid in adults has not been proven.
"Now we are working on finding alternatives," said Lyraki.
Limitation of dissemination
A healthy free-roaming cat lies outside a bakery in Paphos, Cyprus. Stray cats are everywhere on the island - although no one knows how many there are. In response to the FIP outbreak, the Cyprus Veterinary Association, together with ThePetzApp, is launching an initiative to engage cat owners and carers in Cyprus to count the cats in their homes or in the stray cat colonies they care for.
In addition to the immediate situation in Cyprus, there are fears that the strain could spread to other countries or that it is already in other countries from which it has reached Cyprus, as yet unrecognized.
The new strain was confirmed in a cat imported to the UK from Cyprus in August. This cat has been quarantined and is responding to treatment.
Keeping the cats on the island under control can be a challenge. Cyprus is home to many cat rescue activities. Stray cats are regularly collected and taken to other parts of Europe where they are given a new home. According to Epaminondas, there are no regulations regarding the export of cats from Cyprus.
But vets like Lyraki urge rescue groups to be careful. "Our team of experts has issued a recommendation that cats be tested before traveling outside Cyprus and that only cats with negative FCoV antibodies be exported," said Dr. Lyraki. Once the cats arrive at their destination, they should be quarantined for three weeks and then retested for antibodies "until the outbreak is under control and the number of affected cats is significantly reduced."
Meanwhile, Greece, which has its own large stray cat population, has also seen an increase in FIP cases, according to Lyraki.
"We believe that it is only a matter of time before this outbreak spreads to Greece, because Greece and Cyprus are culturally, geopolitically very, very close. There is a lot of exchange and travel between them," she said. "So it's something we're actively monitoring."
Between January and April 2023, the Urolite Center in Minnesota received three shipments of atypical stones (Figure 1). All three samples were obtained from cats. All three cats were under 1 year old. Cats came from North and South America. In each case, the infrared spectrographic pattern of the stones was identical. Urinary stones usually contain large amounts of phosphorus, calcium and magnesium. In these cases, electron dispersion spectroscopy revealed a high proportion of nitrogen, carbon and oxygen.
Mystery solved. When asked about their medical history, all three cats were diagnosed with feline infectious peritonitis. All three were treated with either Remdesivir or its metabolite GS-441524. We requested samples of their antiviral drugs for analysis. The antiviral drugs were spectrographically identical (Figure 2). The stones were composed of GS-441524.
Figure 2: FT-IR spectroscopy of urinary stone of patient and reference sample GS-441524
After administration, GS-441524 is excreted primarily in the urine. Although GS-441524 is very soluble in organic solvents such as DMSO (10-59 mg/ml), it is poorly soluble in aqueous solutions such as water (0.0004 to 0.1 mg/ml). Its limited solubility makes GS-441524 a prime candidate for stone formation. Observation of urinary symptoms in cats receiving Remdesivir or GS-441524 is an indication to look for stones. Observation of atypical crystalluria or uroliths may be an indication to limit the dose of the drug (if possible) and increase water consumption to minimize stone formation.
Analysis of anti-FIP drugs with detected Molnupiravir content
We have received information that several Chinese drug manufacturers, in an effort to reduce the production costs of drugs and their sales price as much as possible while maintaining the largest possible margin, have started to use Molnupiravir (EIDD-2801) as an active ingredient.
The information came from the global group FIP Warriors 5.0, which published several analyzes of drugs declaring GS441524 or GC376 as the active ingredient, but the results of the analyzes show that the drugs contain the already mentioned Molnupiravir. You can see one of the analyzes below. If someone would object that analytics are some means of competitive struggle, it is not so. There were several independent analyses, we also know about the analysis from Bulgaria, one analysis also took place in Slovakia, but the one published by the global FIP Warriors group is the most complex.
Medicines in the CR/SR with the declared content of GS441524 containing EIDD-2801
Figure 1: Suyi 20mg/ml - The manufacturer declares the content of GS441524, but it actually contains Molnupiravir.
This fact also affects our group. One of the drugs where the presence of EIDD-2801 was detected is the widely distributed Suyi brand. The fact that the medicine contains another active substance is not a problem for the person himself. The problem is that the manufacturer hid this fact and declared GS441524 as the active ingredient of their products. This fact should apply to "water" based injectable solutions, which do not sting when applied and whose pH is around 6.
Figure 2: The drug used in the "How we beat FIP" group, for which the manufacturer declares GS441524, but in fact also contains Molnupiravir.
It should be emphasized here that both EIDD2801 and GS441524 are very effective in the treatment of FIP. However, some specifics apply to their use. For example, they have different pharmacokinetics. The one with GS441524 allows application once every 24 hours, while Molnupiravir should be administered twice a day. Anyway, GS441524 is already a very well-proven drug with a minimum of side effects. EIDD-2801 has been used in the treatment of FIP for a shorter time and the official clinical trial is only ongoing, or has not yet been published. That is why other drug manufacturers have so far only recommended it for the treatment of relapses, or in case the cat does not respond to treatment with GS441524. In other words, the drug of first choice is still GS441524. On the other hand, precisely because of the policy of Gilead, which holds the patent for GS441524, hope has dawned for the official treatment of FIP with Molnupiravir, as it has been registered and approved for the treatment of Covid-19 in humans. As a result, a legally available drug (Lagevrio) also appeared in the Czech Republic, but its price was and still is very high and its availability for veterinary use is very complicated.
In an effort to ensure the cheapest possible medicines in order to save as many cats as possible, very cheap medicines also entered our market. The truth is that medication works. We also encountered versions of the solutions that really stung a lot, so it's quite possible that Suyi actually contained GS441524, but over time the manufacturer decided to arbitrarily change the active ingredient, but still declared that it supplied GS441524.
But Suyi is not the only drug containing EIDD-2801 available on our market, about which its manufacturer provided misleading information. In the "How we defeated FIP" group, the drugs from Figure 2 are used.
Why is information about the active substance important?
GS441524 and Molnupiravir have a slightly different mechanism of action. GS441524 acts as a terminator of the viral RNA chain, thereby preventing the virus from replicating. EIDD-2801 integrates into the virus's genome, where it causes an accumulation of virus mutations known as a viral error catastrophe, rendering the virus unable to replicate.
The pharmacokinetics of GS441524 allows application once a day, while EIDD-2801 in oral form should be applied twice a day according to current knowledge. Official information on the frequency of application of the injection form does not yet exist.
GS441524 has already been used for several years in the treatment of FIP, several clinical trials, while the use of EIDFD-2801 in clinical practice is relatively new.
The cytotoxicity of GS441424 is lower than that of EIDD-2801. However, it should be noted here that both substances are safe if the recommended dosage is not exceeded. However, if the dosage is significantly exceeded, side effects may appear in the form of significant neutropenia, drooping/dropped ears, etc.
GS441524 was originally created for injection use, later a tablet form was added. EIDD-2801 was initially intended only for oral use (tablets), while the injectable form was never the subject of a clinical trial. It is only assumed that EIDD and GS have similar bioavailability limits as GS. This means that approximately 50% of the active substance is used for the tablet.
There is a lack of information on the potential side effects of EIDD-2801 in the long term. Considering that the active substance - N4-hydroxycytidine - is a strong mutagen, it is not clear whether after a treatment lasting 12 weeks, which is much longer than the recommended period of 5 days in human medicine, the side effects cannot manifest/accumulate more significantly way.
What is the impact of using another active substance to treat FIP?
Pills In principle, there is no problem with tablets, provided that the content of Molnupiravir corresponds to the stated content of GS. The dosage remains the same, we only recommend dividing the dose calculated for GS into 2x a day. This means, for example, that if you administered 1 tablet of Suyi once a day, you will administer 1/2 tablet twice a day. Actually, even with GS, it is recommended, especially with higher dosages, to administer the medication twice a day.
Injection solutions With them, the situation is a bit more complicated, as the stated concentration of 20mg/ml differs considerably from the measured one (Suyi 40mg/ml, while the real measured concentration of the second solution "Cat rehabilitation nutrition supplement" is up to 70mg/ml). Due to the relatively unclear dosage of EIDD in injectable form and the significantly higher concentration, we recommend not to overdo the dosage. The manufacturer Suyi rejects the accusation regarding the change of the active ingredient.
Previous experience with the use of Suyi medicines
Given that the manufacturer still claims that Suyi products contain GS441524, the drug was used and dosed as GS441524, including application only once a day. After more than 9 months, we can declare that its therapeutic effect is indisputable, we register a large number of cured cases, the price of the treatment is favorable, so it would probably be a hasty decision to stop recommending this medicine. However, due to the manufacturer's attitude, we cannot really guarantee the active ingredient in Suyi products. Again, I emphasize that both GS441524 and EIDD-2801 are effective in treating FIP, so it cannot be said that the drug itself is a scam. Of course, it would be better if the manufacturer, instead of ignoring the analyses, simply and clearly declared the active substance according to reality. Until that happens, it is important that you share your experiences with this medicine. For example, in the form of reviews on the website, or directly in the FIP Warriors CZ/SK group.
We certainly do not want to cause panic with this warning. The truth is that the drop in the price of treatment has made it available even for cases where their owners would otherwise have decided on euthanasia. However, in light of the above findings, it is up to you which medication you decide to use. In any case, pay extra attention to checking/monitoring the cat's condition.
Medicines with directly declared EIDD-2801 content
If the manufacturer openly produces drugs containing EIDD-2801, this is of course a good and serious approach. You can find some medicines containing EIDD-2801 here:
A new strain of feline coronavirus is ravaging the cat population in Cyprus CREDIT: CHRISTINA ASSI/AFP via Getty Images
Experts have warned that Cyprus is at risk of becoming an "island of dead cats" after the outbreak of the feline coronavirus.
Stray and domestic cats have been killed since January by the Feline Infectious Peritonitis (FIP) virus, which is one of the strains of the coronavirus. Experts have warned that "a lot of cats" could die if the virus, which is circulating in Cyprus, reaches Britain.
The country, which is sometimes called the "island of cats", is home to the first evidence of animal domestication. However, there is growing concern over the threat posed by "feline Covid" - which does not infect humans but is usually fatal in felines if left untreated.
"Local vets are reporting an alarming increase in FIP cases, which started in January in the capital Nicosia and spread throughout the island within three to four months," said Dr Demetris Epaminondas, vice-president of the Pancyper Veterinary Association.
Veterinarian Kostis Larkou treats a sick cat at a clinic in Nicosia CREDIT: CHRISTINA ASSI/AFP via Getty Images
In a recent blog post, he added that this was the first "outbreak of this magnitude" ever recorded, with previous cases of FIP generally confined to cat farms. Symptoms include fever, abdominal distension, loss of energy, and sometimes increased hostility. The virus usually affects kittens and young cats.
Professor Danièlle Gunn-Moore, an expert in feline medicine at the University of Edinburgh, told the Telegraph that an outbreak of this scale "has never been seen in history", with reports of dead cats lying on the streets and suspicions that a new one could be emerging. a more deadly strain of FIP. Tests are currently underway to confirm this fact.
She added that local authorities have set up an advisory team, launched a media information campaign and are working to change legislation so that drugs can be used to treat cats, but stressed that no feline should be allowed to leave the country without negative tests.
"There is already some evidence - albeit anecdotal - that the infection may have also appeared in Turkey, Lebanon and potentially Israel. If this virus reaches the UK it could cause the death of many of our cats. It would be heartbreaking. We have to take it seriously."
The country, which is sometimes called the "island of cats", has the oldest evidence of animal domestication CREDIT: CHRISTINA ASSI/AFP via Getty Images
Cyprus is a cat-loving country, and its history has a long history with these furry animals – archaeologists have found evidence of their domestication dating back 9,500 years.
However, locals who feed stray cats on the island report that their regulars are increasingly disappearing as they succumb to the virus. Although only 107 cases have been officially reported, veterinarians and animal rights activists estimate that the true number is much higher.
"Since January, we have lost 300,000 cats [due to FIP]," Dinos Ayioamitis, head of Cats PAWS Cyprus and vice-president of Cyprus Voice for Animals, told Agence France Presse. The island's cat population is estimated at around one million.
He said part of the problem with counting cases is that with so many stray animals living in Cyprus, it is almost impossible to diagnose and document all cases of the disease.
Dr. Epaminondas said that "the only way to stop the disease is treatment," but even that proved difficult.
Experts want to start using the two treatments on cats, but bureaucratic hurdles and costs have prevented further progress.
These are the drugs remdesivir, which is used to treat Covid-19, and the closely related drug GS-441524. Although approved for use on animals in the UK and for import into Cyprus, they are expensive - from £2,500 to £6,000 for a 3-4kg cat.
Experts want to start using two treatments on cats CREDIT: CHRISTINA ASSI/AFP via Getty Images
Another option is a cheaper antiviral used to treat Covid-19 in humans called molnupiravir. Dr Epaminondas estimates it would cost around £170 per animal - but the Veterinary Association's application for permission to treat the cats was rejected in May because the government said human medicines could not be imported for use in veterinary care.
Professor Gunn-Moore urged the Cypriot government to make the drugs GS-441524, remdesivir and molnupiravir available to all cats, but said the ultimate control tool would be a vaccine.
"It's a coronavirus, so based on the Covid epidemic, it could very well happen if pharmaceutical companies want to do it," she said.
With the government taking no action, some people are buying the drugs themselves - and Dr Epaminondas told Cyprus News in May that a black market for cheap, unlicensed drugs was "flourishing".
Among those looking for their own solutions is Vasiliki Mani, 38, a member of several animal welfare organizations who spent around £3,000 from her savings to treat two sick strays. She told AFP that if FIP is not stopped soon, Cyprus will become an "island of dead cats".
Local residents who feed stray animals report that their resident cats are increasingly disappearing as they succumb to the virus CREDIT: CHRISTINA ASSI/AFP via Getty Images
What to do when your cat gets FIP?
A huge outbreak of Feline Infectious Peritonitis (FIP) has raised concerns in Cyprus, particularly with reports that a slightly different version of the virus may be circulating, but is not unique to the country and has previously been reported in the UK.
If your cat shows symptoms such as fever, abdominal distension, loss of energy and sometimes aggressive behavior, experts recommend that you take it to the vet immediately. Kittens and cats under two years of age are most at risk.
An antiviral drug used to treat Covid-19 called remdesivir is available in the UK, as well as a closely related drug called GS-441524, approved for use in cats with FIP.
Veterinarians say that the "gold standard" of treatment is the application of remdesivir in an infusion for three to four days, followed by injections of the drug for up to two weeks. The oral drug GS-441524 is then used to prevent relapse – the total duration of treatment is approximately 12 weeks.
Article provided and translated with permission Danielle Gunn-Moore. Original article: VetRecord, Volume192, Issue 11, 3/10 June 2023, Pages 449-450, published 6/2/2023.
Colleagues and the public are alerted to an outbreak of Feline Infectious Peritonitis (FIP) in Cyprus that broke out in the capital city of Nicosia in January 2023. An increasing number of cases have been reported in the districts of Larnaca, Limassol and Famagusta. Within 12 weeks, the number of PCR-confirmed FIP cases increased more than 20-fold compared to the previous year.
Biopsies of cavitary fluids, abdominal lymph nodes by fine needle aspiration or tissue biopsies of cats with clinical signs consistent with FIP were sent to Vet Dia Gnosis in Limassol. After cytological or histopathological examination, samples were subjected to automated extraction of total nucleic acid and RT-PCR for the detection of feline coronaviruses (FCoV) at Laboklin Bad Kissingen, Germany. 1
Three and four PCR-confirmed FIP cases were reported in 2021 and 2022, respectively, while 98 PCR-confirmed FIP cases were reported from January to April 2023.
Outbreaks of FIP have already been documented in the UK, USA and Taiwan, but only in breeding facilities and trapping centres. 2-4 This outbreak spread very quickly in different districts of the island, with local veterinarians reporting clinical cases even in cats living exclusively indoors. This is extremely alarming and suggests that there is a highly virulent strain of FCoV in Cyprus that can potentially be transmitted by mechanical vectors. We therefore recommend that cats be kept indoors.
Paphos district is geographically the farthest from Nicosia and has not yet seen an increase in cases.
To prevent the spread of this strain of FCoV outside the island, we encourage veterinarians to serologically test every cat before it travels outside Cyprus. No seropositive cat should travel outside of Cyprus until we have a better understanding of the current outbreak. Ideally, if the cat is allowed to travel, it should be kept indoors for 10 to 14 days and retested, as acutely infected cats are likely to seroconvert later. 5
The disease spread very quickly in different districts of Cyprus, indicating that a highly virulent strain of feline coronavirus is present on the island.
Introducing travel measures for cats traveling from Cyprus must be a priority for the UK. This is due to the high number of animals traveling between the two countries, which reflects the existing historical ties; parts of Cyprus are British Overseas Territories and there are significant numbers of British expatriates residing in Cyprus permanently or seasonally. In the past we have seen the introduction of other infectious agents into the UK via dogs traveling from Cyprus, for example Hepatozoon canis and Leishmania infantum. 6
We are currently analyzing FCoV before and during the outbreak, and we are implementing an epidemiological monitoring system. This will provide us with important information regarding this highly virulent strain and help us understand what is causing this epidemic and how we can control its impact on the cat population and the risk of spreading to other countries.
The high number of stray and free-ranging domestic cats in Cyprus is something that could potentially have played a key role in the outbreak, but there are other factors to consider, including the recent introduction of FIP treatment and the recent Covid-19 pandemic.
Charalampos Attipa, senior lecturer in veterinary clinical pathology Danielle Gunn-Moore, professor of feline medicine Stella Mazeri, EBVS European Specialist in veterinary public health Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG email: charalampos.attipa@ed.ac.uk Demetris Epaminondas, vice president of the Pancyprian Veterinary Association Veterinary Services, Ministry of Agriculture, Natural Resources and Environment, Cyprus Maria Lyraki, EBVS European Specialist in small animal internal medicine Vets4Life Referral Hospital, Athens, Greece Alexandros Hardas, lecturer in veterinary anatomic pathology Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, Hertfordshire AL9 7TA Stavroula Loukaidou, veterinary surgeon Vet Dia Gnosis Ltd, Limassol, Cyprus Michaela Gentil, veterinary surgeon Laboklin GmbH and Co KG, Bad Kissingen, Germany
References
Gut M, Leutenegger CM, Huder JB, et al. One-tube fluorogenic reverse transcription-polymerase chain reaction for the quantitation of feline coronaviruses. J Virol Methods 1999;77:37–46
Wang YT, Su BL, Hsieh LE, et al. An outbreak of feline infectious peritonitis in a Taiwanese shelter: epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus. Vet Res 2013;44:57
Barker EN, Tasker S, Gruffydd-Jones TJ, et al. Phylogenetic analysis of feline coronavirus strains in an epizootic outbreak of feline infectious peritonitis. J Vet Intern Med 2013;27:445–50
Healey EA, Andre NM, Miller AD, et al. Outbreak of feline infectious peritonitis (FIP) in shelter-housed cats: molecular analysis of the feline coronavirus S1/S2 cleavage site consistent with a 'circulating virulent-avirulent theory' of FIP pathogenesis. JFMS Open Rep 2022;8:20551169221074226
Stoddart ME, Gaskell RM, Harbor DA, et al. Virus shedding and immune responses in cats inoculated with cell culture-adapted feline infectious peritonitis virus. Vet Microbiol 1988;16:145–58
Attipa C, Maguire D, Solano-Gallego L, et al. Hepatozoon canis in three imported dogs: a new tick-borne disease reaching the United Kingdom. Vet Rec 2018;183:716
When discussing feline coronavirus (FCoV) infection in a multicat setting, it is important to understand the correct terminology. The term FCoV is a collective term for two historically named viruses. A coronavirus was eventually identified as the causative agent of feline infectious peritonitis (FIP) in cats, which was named FIP virus or FIPV (Ward, 1970; Zooket al., 1968). Subsequently, FIPV was found to be a mutant form of FCoV that was present in cats infected with a widespread and minimally pathogenic enteric coronavirus and was named feline enteric coronavirus (FECV) (Pedersen et al., 1981). To avoid misunderstandings, this author prefers to refer to the form of FCoV that applies to the immediate discussion. Therefore, it is appropriate to use the term FIPV when discussing the form of FCoV found in a specific type of white blood cell (monocyte/macrophage) in the affected tissues and body fluids of cats with FIP. The term FECV is used to refer to the form of FCoV that causes chronic and intermittent infections of the epithelium in the lower intestine of healthy cats and is excreted in large quantities in the feces. Enzootic is the correct term for infections that occur in animal populations, while endemic is the corresponding term used for humans. Clinical "signs" are what veterinarians and pediatricians observe during physical examination or what owners/parents communicate to them, while symptoms are what patients describe to their doctors. Therefore, "epizootic" and "symptoms" are not strictly veterinary terms.
FECV, like many other microbial infections in cats, is maintained in the population as a chronic or recurrent asymptomatic infection. FECV is first shed in faeces from around 9–10 weeks of life, coinciding with the loss of maternal immunity (Pedersen et al., 2008). Infection occurs via the faecal-oral route and targets the intestinal epithelium, and primary signs of enteritis are mild or usually inconspicuous (Pedersen et al., 2008; Vogel et al., 2010). Subsequent faecal excretion occurs from the colon and usually ceases after several weeks or months (Herrewegh et al., 1997; Pedersen et al., 2008; Vogel et al., 2010) with the development of immunity. The resulting immunity is notoriously short-lived, and repeated infections are common throughout life (Pearson et al., 2016; Pedersen et al., 2008). A stronger immunity appears to develop over time and cats over 3 years of age have been shown to be less likely to become reinfected and become faecal shedders (Addie et al., 2003). Although the level of exposure to FECV is the primary risk factor for FIP in cat breeds (Foley et al., 1997), the health of the immune system at the time of emergence of mutant FIPV is a major determinant of the occurrence of FIP in any population or group of cats.1
FIP is caused by specific mutants that arise during FECV infection (Poland et al., 1996; Vennema et al., 1995).1 These FlP-causing mutants develop with some frequency in the organism, but fortunately most of them are eliminated by the healthy immune system (Poland et al., 1996).1 Given the relationship between FECV enzootic infection and FIP, it is logical to prevent FIP by minimizing FECV exposure. As “no vaccine can produce better immunity than natural infection” and given what is known about the weakness and short-term nature of natural immunity against FECV (Pearson et al., 2016; Pedersen et al., 2008), it is unlikely that it will succeed to develop effective vaccines against FECV.
Although enzootic FECV infection is not amenable to vaccination, thorough carrier testing and strict quarantine can eliminate FECV in a group of breeding research cats (Hickman et al., 1995). However, FECV is so ubiquitous in nature and easily spread by direct and indirect cat-to-cat contact and on human-borne fomites that the strictest quarantine facilities and procedures are required to prevent its spread. How strict must the quarantine be? Experience with testing and removal in conjunction with quarantine to eliminate and prevent FECV infection is limited to one report (Hickman et al., 1995). FECV was eliminated from a specific pathogen-free breed of cats at UC Davis by removing the virus shedders and rigorously tightening quarantine procedures for the remaining colony (Hickman et al., 1995). Nevertheless, FECV re-entered this colony for several years, despite all attempts to prevent its spread (Pedersen NC, UC Davis, unpublished, 2022). The only example of effective quarantine for FECV was described for cats in the Falkland Islands (Addie et al., 2012). These islands in the remote South Atlantic have fortunately remained free of FECV, probably due to their extreme isolation. Measures have been taken to prevent future inadvertent introduction of FECV to the islands (Addie et al., 2012). Based on this experience with feline and murine enteric coronaviruses, it is unlikely that FECV could be kept out of any group of domesticated cats with anything less than the strictest isolation and infection prevention practices.
An interesting approach to prevent or delay FECV infection in kittens in breeding centers has been referred to as "early weaning and isolation" (Addie et al. 19952). It was based on the finding that kittens born to FECV-exposed or infected mothers have maternal immunity to infection up to 9 weeks of age (Pedersen et al., 2008). Therefore, kittens weaned a few weeks before the loss of this immunity (4-6 weeks of age) are usually free of infection and, if removed from the mother and isolated from other cats, could theoretically be kept virus-free. This practice was initially popular, but the necessary facilities and quarantine procedures required to prevent later infection were difficult to maintain in kennels with larger numbers of breeding cats (> 5 cats, Hartmann et al., 2005; > 10 cats Addie et al., 19952). Therefore, elimination of FECV in kittens by early weaning and isolation has been doomed to failure in most common homes/kennels due to the largely unavoidable exposure to FECV that occurs in the breeding, rearing and exhibition of breeding cats.
Another problem with early weaning and isolation is the need to separate virus-free kittens from other cats in a large group. This problem could be avoided if all the cats could get rid of the infection at the same time. This can be achieved by serially testing faeces for FECV excretion over a period of time and culling all shedding cats. However, since a significant proportion of cats in farms involved in FECV enzootic disease shed FECV in their faeces (Foley et al., 1997; Herrewegh et al., 1997), culling cats can have a serious impact on the gene pool (Hickman et al., 1995). . This begs the question – can FECV be eliminated in all cats in a group at the same time? Interestingly, the relatively recent discovery of effective antivirals against FIP has also provided a possible method of eliminating all the spreaders of the virus at the same time (Pedersen et al., 2018, 2019). Early studies of such use of antivirals such as GS-441524, although of a rather preliminary nature, suggest that FECV can be eliminated from a closed population of cats with relatively short treatment (Addie et al., 2023).
Assuming that FECV can be eliminated as an enzootic virus from the feline population by using specific antivirals, what are the pitfalls of doing so? The first pitfalls are the cost of antivirals, the frequent testing of feces required to identify shedding animals, and the establishment and maintenance of adequate quarantine facilities and practices. Therefore, domestic facilities with poor barrier isolation practices are doomed to failure to maintain this group of cats FECV-free for extended periods of time. The second pitfall is related to the normal activities of breeding and exhibiting breeding cats. Breeding cats involves frequent interaction between the cats as well as humans in contact with the cats and with each other. It is also difficult to imagine that a breeder and avid show participant would give up all the joys of breeding and showing their cats by avoiding all such interactions. The final question is: "Now that the cats are free of FECV, what are you going to do with them?". What is the chance that they will remain without FECV for any length of time after leaving the controlled environment? They will have no immunity to FECV and will be very sensitive to the slightest exposure. The same will apply to the group of cats they come from. Finally, the continuous antiviral treatment required to maintain a group of cats free of FECV infection is likely to result in the development of drug resistance. We now know that resistance to GS-441524 can occur in cats treated for FIP, and UC Davis researchers1 and Cornell University3 agree that acquisition of drug resistance in enzootic FECV infections would outweigh any potential benefit of such treatment on FIP incidence. FIP is currently curable in more than 90 % cases4 and even if resistance to antivirals does develop, it is largely confined to the affected cat. It can be argued that HIV-1 infection in humans is currently prevented by antivirals without any reported concerns about drug resistance. Preventive treatment of HIV-1 however, it is not a monotherapy, but includes several drugs of different classes.3 This is not done to increase the effectiveness of treatment, but rather to prevent drug resistance. If the virus develops resistance to one drug in the drug mix, the other drugs will prevent it from replicating.
In conclusion, I would like to paraphrase: "Just because something can be done, should it be done?" The author believes that much larger and better designed studies, conducted over a long period of time, are needed before this practice can be seriously considered. The overall incidence of FIP in smaller and well-maintained farms with enzootic FECV infection is usually less than 1 %, and currently more than 90 % cases of FIP that might arise can be cured.4 A practical way to reduce the incidence of FIP is to keep the number of breeding cats and kittens low, to keep more older cats, to not breed individuals and bloodlines that have given rise to cases of FIP, and to minimize the stress of frequent introductions of new cats and changes in placement or relocated.1 In smaller farms, isolation and early weaning can also be useful.
References
Addie DD, Bellini F, Covell-Ritchie J, Crowe B, Curran S, Fosbery M, Hills S, Johnson E, Johnson C, Lloyd S, Jarrett O. 2023. Stopping Feline Coronavirus Shedding Prevents Feline Infectious Peritonitis. Viruses. 15(4), 818.
Addie DD, Schaap IA, Nicolson L, Jarrett O, 2003. Persistence and transmission of natural type I feline coronavirus infection. Journal of General Virology 84, 2735-2744.
Addie, D.; Jarrett, O. Control of feline coronavirus infections in breeding catteries by serotesting, isolation, and early weaning. 1995. Feline Pract. 23, 92-95.
Foley JE, Poland A, Carlson J, Pedersen NC, 1997. Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. J Amer Vet Med Assoc. 210, 1313-1318.
Hartmann K, 2005. Feline infectious peritonitis Vet Clin North Am Small Anim Pract. 35(1), 3979.
Herrewegh AAPM, Mahler M, Hedrich HJ, Haagmans BL, Egberink HF, Horzinek MC, Rottier PJM, de Groot RJ, 1997. Persistence and evolution of feline coronavirus in a closed cat-breeding colony. Virology 234, 349-363.
Hickman MA, Morris JG, Rogers QR, Pedersen NC, 1995. Elimination of feline coronavirus infection from a large experimental specific pathogen-free cat breeding colony by serologic testing and isolation, Feline Practice 23, 96-102.
Pearson M, LaVoy A, Evans S, Vilander A, Webb C, Graham B, Musselman E, LeCureux J, VandeWoude S, Dean GA, 2019. Mucosal Immune Response to Feline Enteric Coronavirus Infection. Viruses 11, 906.
Pedersen NC, Theilen G, Keane MA, Fairbanks L, Mason T, Orser B, Che CH, Allison C, 1977. Studies of naturally transmitted feline leukemia virus infection. American Journal of Veterinary Research 38, 1523-1531.
Pedersen NC, Boyle JF, Floyd K, Fudge A, Barker J, 1981. An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis. American Journal of Veterinary Research 42, 368-377.
Pedersen NC, Allen CE, Lyons LA, 2008. Pathogenesis of feline enteric coronavirus infection. Journal of Feline Medicine and Surgery 10, 529-541.
Pedersen NC, Liu H, Dodd KA, Pesavento PA, 2009. Significance of coronavirus mutants in feces and diseased tissues of cats suffering from feline infectious peritonitis. Viruses 1, 166-184.
Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, Bannasch M, Meadows JM, Chang KO, 2018. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. Journal of Feline Medicine and Surgery 20, 378–392.
Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, Bannasch M, Meadows JM, Chang KO, 2018. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. Journal of Feline Medicine and Surgery 20, 378–392.
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Although currently the most widely used active substance in the treatment of FIP is the nucleoside analog GS-441524, in fact there are already several agents with antiviral activity that can be successfully used in the treatment of FIP. In this article, I would like to introduce you to currently used antivirals, or recommendations for their use.
Due to the absence of clinical studies other than GS-441524 and GC-376, unless otherwise stated, the recommended duration of treatment for FIP is still 12 weeks. This does not mean that the treatment cannot be shorter for a specific individual, but at the same time there are also cases where the treatment must be extended. It should also be noted that the treatment should always be terminated only after the assessment of the cat's clinical condition and the results of the blood test.
GS-441524
Currently the most widely used antiviral drug for the treatment of FIP. Nucleoside analog GS-441524 has been the subject of several clinical studies. The first to prove its effectiveness in the treatment of FIP was Dr. Niels Pedersen and his team. You can find his pioneering clinical study here. The subject of this clinical study was injection form active substance, but it didn't take long, and tablet forms of the drug also appeared on the market. The originally determined dosage was gradually increased over time along with the decreasing price of the treatment, and nowadays it is good to stick to the values listed below. In addition, GS-441524 is a very safe antiviral, and because of minimizing the risk of relapse, it is better overdose, such as underdosing.
Unfortunately, the patent holder of GS-445424, Gilead, never licensed it to another company (with the exception of Bova), and is not even trying to commercialize this substance. For this reason, practically all medicines containing GS-441524 come from the black market.
In the case of a severe condition, it is possible and even advisable to use at least the first 3 days of the so-called booster dosage at the dosage level for neurological FIP, even if the cat does not have neurological FIP. There are even opinions that it is good to use neurological dosage for the first 14 days even in non-neurological forms of FIP (Dr. Addie).
FIP type
GS-441524 - injection solutions
Wet FIP (abdominal effusion, without ocular and neurological symptoms)
6 mg/kg once a day sc
Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms)
8 mg/kg once daily SC
Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.)
10 mg/kg once daily SC
Neurological FIP (neurological symptoms, eg anisocoria or mydriasis)
12 mg/kg once daily SC
Relapse of FIP (usually associated with neurological manifestations)
15 mg/kg once daily SC
Arrival tablets got a little confused with the dosage during treatment, because some manufacturers started to list the so-called equivalent GS content so that the dosage used is "compatible" with injections, while other manufacturers state the real GS content. It is believed that the oral bioavailability of the drug is only about 50% compared to injections, so in practice it is necessary to count on twice the dosage of such tablets compared to injections, or simply use tablets with a known real GS content as tablets with a half-equivalent GS content. There is only one company licensed to use GS-441542 in tablet form in veterinary practice, and that is the British company Bova. Its GS 50 mg tablets are used for the legal treatment of FIP in Australia and the UK. Unfortunately, they are very expensive. It is necessary to take into account the price of 1 tablet approx. 1000 CZK. For this reason, similar to injectable solutions, tablets from the Chinese black market are mainly used for treatment.
Note that for neurological FIP, the recommendation is to split the dose twice a day. This is due to the presumed reduced absorption capacity of the drug in the digestive tract at an equivalent dosage higher than 10mg/kg.
FIP type
GS441524 - tablets with the specified real GS content
GS441524 - tablets with the stated equivalent GS content
Wet FIP (abdominal effusion, without ocular and neurological symptoms)
10-12 mg/kg once a day
6 mg/kg once a day
Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms)
12-16 mg/kg once a day
8 mg/kg once a day
Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.)
20 mg/kg once a day or 10 mg/kg twice a day
10 mg/kg once a day or 5 mg/kg twice a day
Neurological FIP (neurological symptoms, eg anisocoria or mydriasis)
12 mg/kg twice a day
6 mg/kg twice a day
Relapse of FIP (usually associated with neurological manifestations)
15 mg/kg twice a day
7.5 mg/kg twice a day
As already mentioned, GS-441524 is a safe antiviral, but on the other hand, neutropenia is very often observed after treatment, which can last for a very long time (up to several months). In the case of long-term and very significant neutropenia, the application of filgrastim - a factor that stimulates the formation of hematopoietic cells - can be considered.
GC376
Protease inhibitor GC376 is actually a first generation anti-FIP drug. Its effectiveness has been proven in the treatment of wet and dry FIP, but due to the significantly reduced ability to penetrate through the blood-ocular and blood-brain barrier, it is not suitable for the treatment of ocular or neurological forms of FIP. Given that very shortly after pilot study GC376 was lost to Dr. Niels Pedersen with the nucleoside analog GS-441524, the importance of the protease inhibitor GC376 has declined significantly. However, it turns out that it can be, and probably will be in the future, an important component of the combined treatment of FIP, for example together with GS-441524, where the effect of both active substances is mutually potentiated, and as a result is much more pronounced than with each active substance alone . Currently, the company is trying to launch GC376 on the market Anivive.
FIP type
GC376 - solution for injection
Wet FIP (abdominal effusion, without ocular and neurological symptoms)
15 mg/kg 2x daily sc
Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms)
15 mg/kg 2x daily sc
Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.)
it is not used
Neurological FIP (neurological symptoms, eg anisocoria or mydriasis)
it is not used
Relapse of FIP (usually associated with neurological manifestations)
it is not used
GC376 is a safe antiviral, but its most significant side effect is a delay in the development of permanent teeth in young cats.
Remdesivir
This is another drug from Gilead. In fact, it is the so-called prodrug of the above GS-441524. After the application of remdesivir, intracellular metabolism to GS-441524 occurs in the organism. Remdesivir was marketed by Gilead under the trade name Veklury and has played a significant role in the treatment of Covid-19 in humans. However, its use in veterinary practice is very questionable and impractical. Firstly, it lacks approval for veterinary use and secondly, it is very expensive. Application is also a weak point of the drug, as it is intended for intravenous administration. The concentration of Veklura after reconstitution is only 5mg/ml.
The company Bova managed to obtain a license for the use of remdesivir for veterinary use and produces a product with a concentration of 10 mg/ml, which can be used in the form of subcutaneous injections. Unfortunately, the price is very high, so it is not used much in common practice. Remdesivir has approximately 2x the molecular weight of GS-441524, so the dosage of remdesivir must be approximately 2x higher than that of GS-441524.
FIP type
Remdesivir - solution for injection
Wet FIP (abdominal effusion, without ocular and neurological symptoms)
10-12 mg/kg once a day iv/sc
Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms)
10-12 mg/kg once a day iv/sc
Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.)
15 mg/kg once daily iv/sc
Neurological FIP (neurological symptoms, eg anisocoria or mydriasis)
20 mg/kg once a day iv/sc
Relapse of FIP (usually associated with neurological manifestations)
25 mg/kg once a day iv/sc
Molnupiravir
Antiviral with a long history primarily intended for the treatment of Covid-19 in humans. Molnupiravir (EIDD-2801) is incorporated into the genome of RNA viruses and causes random mutations resulting in the so-called virus bug disaster. The drug exists in the form tablets or capsules. Most legally manufactured drugs (e.g. Lagevrio) contain capsules containing 200 mg of the active substance, and re-encapsulation of the drug is necessary for use in the treatment of FIP. Of course, Chinese manufacturers also produce tablets intended for direct use in animals. Although molnupiravir is not strictly the drug of first choice in the treatment of FIP, it shows great potential in the treatment of FIP relapses, resistance to GS-441524, or can be an important part of FIP combination therapy.
FIP type
Molnupiravir
Wet FIP (abdominal effusion, without ocular and neurological symptoms)
10 mg/kg twice a day
Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms)
10 mg/kg twice a day
Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.)
12 mg/kg twice a day
Neurological FIP (neurological symptoms, eg anisocoria or mydriasis)
12 mg/kg twice a day
Relapse of FIP (usually associated with neurological manifestations)
15 mg/kg twice a day
With molnupiravir, as with GS-441524, neutropenia can often be observed after the end of treatment, especially at high dosages.
Mefloquine
Mefloquine is an interesting substance that has its primary application in the treatment of malaria in humans. It is not effective as a monotherapy in the treatment of FIP, but it is shown that it can play an important role in the adjunctive treatment of FIP, for example with GS-441524. It mainly makes it possible to reduce the price of FIP treatment or reduce the risk of relapse. The normal length of treatment using GS-441524 is about 12 weeks, but in principle it is possible to shorten this treatment to about 8 weeks and use mefloquine for the next 4 weeks. In Europe, mefloquine is available under the trade name Lariam. One tablet contains up to 250 mg of active substance. In practice, the drug is administered at a dose of 12.5 mg/kg twice a week, or 62.5 mg twice a week for one cat. This corresponds to 1/4 tablet of Lariam twice a week (for example, Monday and Thursday). Lariam must be given with food, otherwise there is a higher probability of the cat vomiting.
I strongly reiterate the fact that mefloquine is not intended for the treatment of FIP as a monotherapy, and should always follow as a supplement after the treatment of FIP with one of the above-mentioned antivirals, or in combination with them.
FIP type
Mefloquine (Lariam)
Wet FIP (abdominal effusion, without ocular and neurological symptoms)
62.5 mg per cat twice a week
Dry FIP (without effusion, or with effusion in the chest cavity without eye and neurological symptoms)
62.5 mg per cat twice a week
Ocular FIP (ocular symptoms - cloudy eye, blood in the eye chamber, etc.)
62.5 mg per cat twice a week
Neurological FIP (neurological symptoms, eg anisocoria or mydriasis)
62.5 mg per cat twice a week
Relapse of FIP (usually associated with neurological manifestations)
62.5 mg per cat twice a week
Other antivirals
It turns out that there is actually up to several dozen of potentially suitable antivirals applicable to the treatment of FIP. Unfortunately, no clinical studies have yet been conducted for many of them, which are important not only for the verification of effectiveness, but mainly for the determination of cytotoxicity. The goal, of course, is to cure the animal without causing poisoning or other health problems that would lead to the cat's death.
Combined therapies
The currently used FIP treatment usually takes the form of monotherapy, that is, the drug contains only one active substance. Unfortunately, this approach has the disadvantage that it is only a matter of time before resistance to the used antiviral begins to manifest itself. The way out of this situation is combined therapy, when 2 or more antivirals are used simultaneously for the treatment of FIP. It is not an entirely simple issue, as in some combinations the therapeutic effect is significantly strengthened, but there are also combinations where, on the contrary, the therapeutic effect is weakened. Currently, the most likely drug combinations are the pairs GS-441524 and Molnupiravir, or GS-441524 and GC376. Regarding the second named combination, it has already taken place in China study, the result of which is really encouraging. In addition to curing all cats, the treatment time was reduced from 12 weeks to 4 weeks. It turns out that a dosage of GS-441524 5mg/kg/24h and GC-376 20mg/kg/12h could be used to achieve a therapeutic effect. However, this combination therapy still needs further independent verification of efficacy.
As the name suggests, this is not about FIP, but it's important to know. I registered the strange information that when treating FIP with molnupiravir, it was also possible to cure FIV. And that cats that were positive before treatment were negative for FIV after treatment. And that the tests were not quick tests, but tests from Laboklin...
Apparently, many of you have the misconception that if something comes from a lab, that automatically means there is a clear answer. But it is a huge mistake. Let's talk about the principle of FIV and FeLV testing. Rapid tests (snaptests) are antibody-based for FIV and antigenic for FeLV. And here is the basic stumbling block. Antibodies, even if there is some miraculous cure, do not disappear after treatment. Antibodies are proteins produced by the immune system and their purpose is to identify and neutralize foreign objects in the body. So the very negative result of the proilase test after the treatment, before which the test was positive, means only one thing - One of the two tests was false positive (or false negative) and therefore defective.
It is for this reason that it is strongly recommended, especially in the case of a positive FIV or FeLV test, to perform a confirmation test using another laboratory method.
And why did I say that the fact that something is done in the laboratory does not necessarily mean anything? Simply. If you have the FIV and FeLV test done by a laboratory and do not specify the method, it is very likely that the laboratory will do a SNAP test or an ELISA (EIA) test. You can tell by the price of the test, but also by what is on the report. The image below shows that this was a test FIV AK, but what does it mean? antibody test (AK=Antikörper). In parentheses is EIA, which stands for “enzyme-linked immunosorbent assay”. The abbreviation ELISA is also used. You should know that the gold standard of the confirmation test for FIV is the method test Western Blot... In that case, it would be mentioned in the report like this. Although the WB test is also an antibody test, it works on a completely different principle. For FeLV, the standard PCR is used as a confirmatory test. And something else. Why do you think you will test positive for FCoV antibody after treatment for FIP? Exactly for the reason I wrote about above. Antibodies remain in the body after treatment for FIP and this is completely natural. Even after you are cured of the much-maligned Covid, you will still have antibodies. Otherwise, it would be very bad for you. And ask yourself why FCOV antibodies would remain after treatment and FIV antibodies would disappear? Antibodies remain in the body for several months after treatment, and in some cases or for incurable diseases such as FIV, even for years.
In the picture you can see an FIV antibody test with a negative result, which led the cat's owner to the fantastic but unfortunately premature conclusion that the FIV was cured by treating the FIP.
For the sake of completeness, I am also attaching an FIV test using the Western Blot method for my cat, which unfortunately confirmed that it is FIV positive. And we even had a few snap tests done before (one even in the laboratory), some of which were negative and some were positive.
Please stop jumping to conclusions and tame the euphoria about the FIV cure. The result of two antibody tests with a conflicting result does not mean that a cure has occurred, but that one of the tests showed a faulty result.
In addition to the above information, you should also be aware that after vaccination based on the principle of an inactivated virus, it is no longer possible to use antibody tests for the diagnosis of the given disease, because the vaccination serves precisely to make the body create antibodies.
Antibody tests can come out positive even in the case of young kittens (under 20 weeks), when they can have maternal antibodies from breast milk and subsequently the tests can be negative.
Regarding PCR testing for FIV, I would add that you should read the article https://www.fivcats.com/FIV/fiv_testing.html, where the basic principles of FIV tests and their reliability are presented. You will learn, for example, that the error rate of negative PCR tests is really very high.
FIV treatment ???
The FIV virus is a retrovirus related to the virus that causes HIV (AIDS). The main problem is that the virus is "built-in" into the host's genome, and that is why such a disease is not curable. Of course, this does not mean that the life expectancy of an affected individual cannot be extended with the use of symptomatic therapy. If an FIV cat is affected by an infection, antivirals can help, if a bacterial infection appears, ATB is used... Thus, accompanying diseases and infections are dealt with, and with this treatment, the FIV disease itself is kept under control, but it is not cured. To be sure, I also asked those actually called about the possibility of FIV treatment with molnupiravir. Answers by Danielle-Gunn Moore - professor of feline medicine from the University of Edinburgh and Yunjeong Kim - professor at Kansas State University, who together with Dr. Pedersen is behind the discovery of the treatment of FIP using GS-441524, hopefully they will convince those who got "drunk" on the croissant and succumbed to the vision of treating FIV with molnupiravir.
Translation: “Retroviruses such as FIV or HIV (AIDS) are not treatable with antivirals because the viruses are embedded in the host's genome. If there is a good antiviral for FIV, it can help the cat stay symptom-free for a longer period of time (similar to HIV drugs in humans), but I don't think there is any evidence that molnupiravir is effective against FIV.”
Translation: "It was pointed out to me that molnupiravir, because it works on the replicating virus, will never cure FIV, just like the effectiveness of these HIV drugs, because the proviral non-replicating virus can never be their target. Even HIV always requires 3-4 drugs, occasionally 2 – just to keep it under control, so really no chance of a cure.”
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