Dr. Pedersen on the relationship between Remdesivir and GS441524

Original article: SOCKFIP

Dear veterinarians, cat owners and the public,

I am still asked about the relationship between GS-441524 and the very promising treatment for Covid-19 - Remdesivir. GS-441524 is a biologically active ingredient in Remdesivir and has been commonly used worldwide for the safe and effective treatment of feline infectious peritonitis (FIP) for over 18 months. FIP is a common and fatal coronary heart disease in cats. GS-441424 and Remdesivir are almost identical drugs. Remdesivir is a form of GS-441424 that Gilead Sciences has decided to use in humans to treat COVID-19, and clinical trials are currently underway in China, the United States, and several other countries. Remdesivir is called product. The prodrug is transformed by infected cells into the active ingredient, which in this case is GS-441524 with the addition of one phosphate group (i.e. GS-5734). Gilead researchers slightly modified GS-5734 to protect the added phosphate group and allow absorption into the cells. This form of GS-441524 is known as Remdesivir. Upon entering the cell, its enzymes remove protection to give GS-5734. GS-5734 is further activated in the cells by the addition of two additional phosphates to form the triphosphate form GS-441524. This is a molecule that inhibits the production of viral RNA. We decided to use GS-441524 to treat FIP because it had the same antiviral properties as Remdesivir and at that time Gilead Sciences did not anticipate its use in humans. GS-441524 is also much cheaper than Remdesivir. Therefore, there was no apparent conflict between the use of one form for cats and another form for humans. However, Gilead believed that our research on cats would affect the approval of Remdesivir for use in human medicine and refused to allow GS-441524 for the treatment of animals. This refusal, coupled with the desperate need for FIP treatment worldwide, led to the Chinese black market for GS-441524. FIP is a major problem for domestic cats in China, and Chinese cat owners have demanded FIP treatment even more desperately than owners in other countries. The first papers describing the treatment of FIP with GS-441524 were published in 2018 and 2019, and thousands of cats have since been treated. Despite this experience, the medical community, including researchers, was apparently unaware of the use of GS-441524 to treat FIP and its relationship to Remdesivir. Veterinarians have considerable but underappreciated experience with coronaviruses, coronavirus diseases and vaccines in pigs, calves and poultry. Ferrets also suffer from a serious FIP-like disease caused by their own coronavirus species. What happens to GS-441524 for cats if Remdesivir is shown to be safe and effective in treating Covid-19? GS-441524 is the first critical step in the production of Remdesivir and it is logical to assume that it will lead to the existence of competition in its use for cats and humans. On the positive side, the worldwide approval of Remdesivir may also help to change the opposition to the granting of rights to use GS-441524 in animals. If Remdesivir were approved for human use (although not approved by GS-441524 itself), it could also become legally available for use in veterinary medicine. However, the safety and efficacy of Remdesivir for the treatment of FIP have not been established.

-Niels C. Pedersen, DVM, PhD, School of Veterinary Medicine, UC Davis ..

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