I am being increasingly questioned about the relationship of GS-441524 and a very promising treatment for Covid-19, Remdesivir.GS-441524 is the biologically active component of Remdesivir and has been widely used around the world to safely and effectively cure cats of feline infectious peritonitis (FIP) for over 18 months. FIP is a common and highly fatal coronavirus disease of cats. GS-441424 and Remdesivir are almost identical drugs. Remdesivir is the form of GS-441424 that Gilead Sciences has chosen to use in humans for COVID-19 and is now in clinical trials in China, USA and several other countries. 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. We chose to use GS-441524 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. Therefore, there was no apparent conflict with using one form for cats and another form for humans. However, Gilead came to believe that our cat research would interfere with their ability to get Remdesivir approved for humans and refused to grant animal rights for GS-441524. This refusal, coupled with the desperate need around the world for the treatment of FIP, led to a Chinese black market for GS-441524. FIP is also a significant problem in pet cats in China, and Chinese cat owners were even more desperate for a treatment for FIP than owners in other countries. The first papers describing GS-441524 treatment of cats with FIP were published in 2018 and 2019 and thousands of cats have been treated since then. In spite of this experience, the medical profession, including researchers, have been seemingly unaware of the use of GS-441524 for a coronavirus disease of cats and its relationship to Remdesivir. Veterinarians also have considerable experience with coronaviruses, coronavirus diseases, and coronavirus vaccines for swine, calves and poultry that has gone unappreciated. Pet ferrets also suffer a severe FIP-like disease caused by their own species of coronavirus. What will happen to supplies of GS-441524 for cats if Remdesivir is proven to be safe and effective as a treatment for Covid-19? GS-441524 is the first critical step in the production of Remdesivir and it is logical to assume that there will be a competition between cats and humans for it. On a positive note, worldwide approval for Remdesivir may also help change minds against granting animal rights for GS-441524. If approved for human use, Remdesivir, if not GS-441524, would become “legally” available through veterinarians. However, the safety and efficacy of Remdesivir for FIP has not been established.
-Niels C. Pedersen, DVM, PhD, School of Veterinary Medicine, UC Davis.
Note: There is a desperate need for these drugs, but the demand has gotten way ahead of the procedures necessary to bring them safely and economically to the marketplace. It takes 2-7 years to get approvals and market a drug after it is researched in Western countries and the worldwide problems with FIP are only getting worse. This is especially true in advancing countries where the demand for purebred kittens has gone through the roof and the conditions favoring FIP have gone with it. GC376 and GS-441524 are being illegally produced in China and sold through subsidiaries in Europe and US. Manufacturers and secondary suppliers often state that these drugs are to be used for research purposes only, not for human use, or not for veterinary or human applications. However, they are well-aware of their great demand and willingness of many cat owners to pay a high price. The purity or biological activity of these drugs is not assured, and veterinarians (or owners) have no prior experience with preparing them for treatment or using them to treat cats with FIP. The ethical aspects of using black market drugs, even if purchased by owners, is a problem that veterinarians have to confront. Ethical considerations have led many owners to treat their cats without veterinary input, which is unfortunate as the treatment is long, not without side-effects, and must be carefully monitored with regular blood tests.
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