What is GS-441524?

GS-441524 is a nucleoside analog commonly used as an antiviral drug which was developed by Gilead Sciences. It is the active form which the antiviral prodrug remdesivir is converted into inside the body. GS-441524 has also been researched in its own right, as a treatment for feline infectious peritonitis (FIP), a lethal coronavirus disease which affects domestic cats.

GS-441524 was chosed for treatment of the coronavirus disease FIP because it had identical antiviral properties to Remdesivir and at the time was not under consideration by Gilead Sciences for use in humans. GS-441524 is also much cheaper to make than Remdesivir.

Since FIP is usually fatal and there are no approved treatments available, GS-441524 has reportedly been sold on the black market and used by pet owners to treat affected cats, despite not having been officially approved for veterinary use.

GS-441524 and Remdesivir (GS-5734)

Remdesivir is what is known as a prodrug. A prodrug is altered by infected cells to yield the active ingredient, which in this case is basically GS-441524 with the addition of one phosphate group (i.e. GS-5734). 

Gilead scientists slightly altered GS-5734 to protect the added phosphate group and allow absorption into cells. This form of GS-441524 is what is known as Remdesivir.

Once in the cells, cellular enzymes remove the protection to yield GS-5734. GS-5734 is further activated by the addition of two more phosphates in the cells to the triphosphate form of GS-441524. This is the molecule that inhibits the production of viral RNA. 
GS-441524 and GS-5734

How GS-441524 is Curing FIP? (mainly cited from www.fiptreatment.com)

Prior to February 2019,  feline infectious peritonitis (FIP)  was a guaranteed death sentence to cats.  Thanks to a lifetime of dedication and devotion, Dr Niels Pedersen of UC Davis discovered the cure for FIP: the nucleoside analog GS-441524, also referred to as “GS”. 

If a cat’s immune system is healthy and mature, the white blood cells should fight off an infection or virus, and allow the cat to build up an immune response, or antibodies.  Cats who develop FIP have an immune defect or deficiency that causes the white blood cells to replicate, rather than fight, the virus. Essentially, the cats immune system is spreading the virus throughout the cat’s body rather than trying to eliminate it.  Cats who have no immune response develop wet FIP, while cats who have a partial immune response develop dry FIP. 

The nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase.  In layman’s terms, GS441524 interjects itself into the chain reaction and stops the replication of the virus.  

Course of GS-441524 Treatment

Dr Pedersen’s case study determined that a successful course of treatment with GS-441524 is 12 weeks, administered daily.  Some owners have stopped treating once blood work and diagnostics returned to normal; however, the few cats who did relapse were among those who stopped prior to the 12 week protocol.  Because the course of treatment is both emotionally and financially taxing, most owners currently using GS opt to pursue the full 12 weeks, to ensure the highest probability of success.  Cats who undergo the full 12 weeks and remain symptom-free for 90 days following conclusion of treatment are officially cured of FIP.  

GS441 comes in both injectable form, and as of June 2019, a pill form.  Both are administered daily and the dose is based on the weight of the cat. 

For wet & dry FIP without neurological or ocular symptoms, the recommended dosage is 5mg (GS) x weight (kg) / GS concentration per 1mL = dose per 24 hr.  Neurological and Ocular FIP cats require 7mg/kg MINIMUM, and can go as high as 10mg/kg for extreme ocular or neurological cases.

A dosing calculator can be found here.

It is important to note that the dosage should not be reduced during the course of treatment, regardless of how well the cat is responding.  Conversely, if the cat is not responding to the starting dosage, it is safe to increase. It is also crucial to check the cat’s weight often, and adjust the daily dose accordingly. 

The only known side effect of GS-441524 is skin lesions or burns, due to the acidity of the solution (injectable form). For this reason, it is recommended to always clean the cat’s skin after giving an injection.  Many owners also opt to give oral CBD oil or Hemp oil 30-60 minutes before injecting, to help minimize the stress.  Should you opt to do this, it is critical that the product be veterinary grade and the proper dose should be determined by a veterinarian. CBD and/or hemp oil can be fatal to a cat if not administered properly.  More commonly, Gabapentin, a mild pain medication can be given orally 60-90 minutes prior to the injection. The vast majority of cats using GS tolerate the injections just fine without the need for any pain medication or sedative.  

Supportive Care

While we’ve seen first hand that GS is a miracle drug, it’s not the end-all-be-all.  You still need to support your cat’s well-being while waiting for GS to arrive and until your cat starts to respond to it.  Proper supportive care can make all the difference as to whether or not the cat survives. Lack of proper supportive care can cause further complications, up to and including death. 

Cats need to consume minimally 200 calories per day and 60 ml of water per day. Anemia needs to be treated, whether via B12 or possibly a transfusion, depending on severity.  Fluids may need to be drained. Fevers need to be monitored and reduced.  For additional information about crucial home care and supportive care of FIP cats, please continue here.  

Supplemental Care When Using GS-441524 to Cure FIP

In general, unless the cat has a secondary or underlying condition besides FIP, all prescription medications can be stopped once treatment with GS begins.  However, all cats, FIP or not, can benefit from a high quality probiotic such as Fortiflora. A healthy gut is essential in fighting FIP and can help stave off so many other illnesses too.   

For additional information on overall wellness and support, please view the vitamins and supplements page.  

Palliative Care for Cats With FIP

We understand that there are many reasons why someone may not want to use GS-441524.  While it is highly effective, it is also still experimental and in many circumstances, cost prohibitive.  

For those who wish to provide palliative treatment to their FIP cat, there are several options available. 

Polyprenyl Immunostimulant

Polyprenyl Immunostimulant, or “PI” as it is commonly referred to in the FIP groups, is an oral supplement that is administered daily for 1-2 weeks, then every other day once the jump-start dose is completed.  PI is approved to treat feline herpes; however, it is used off-label to treat feline infectious peritonitis.  It is not a cure of FIP, but there have been some long term FIP survivors.  PI is best suited for dry FIP, and the success rate (defined as surviving 1 year or more) is approximately 10%.  

Polyprenyl is used to enhance and strengthen the cat’s immune system, ideally to allow the cat to fight off the virus. 

Cats who are using Polyprenyl should also be receiving overall systemic support by way of weekly B12 injections, daily B12 supplements, and if and as needed, appetite stimulants and ant-nausea medication.  Typically an anti-viral medication will also be prescribed for 10-14 days. 

PI must be prescribed and ordered by a veterinarian. The necessary forms and ordering information can be found on Vet Immune’s website

*Cats who are taking Polyprenyl for FIP should NOT be taking steroids, as steroids will weaken the cat’s immune system and work against the PI. 

Prednisolone / Steroid Treatment for FIP

For many years, steroid treatment was the only option for FIP cats.  It is entirely palliative in nature, i.e. it’s purpose is to keep the cat comfortable for however much time he/she has left.  

Steroids are inexpensive and can help provide temporary comfort to an FIP cat by increasing appetite, reducing fever, reducing inflammation, and with wet FIP, steroids may also help to reduce the effusion.

Home Care/Supportive Care

The success of palliative care, as well as your cat’s quality of life, depends highly on supportive care and treating symptoms such as inappetence, fever, anemia, diarrhea and more.  Please continue reading about supportive care here.