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GS-441524 is substantially less toxic than remdesivir, far easier to synthesize, more soluble, and has essentially identical effects because remdesivir is apparently metabolized into it (in spite of having been designed to take a different route). https://www.statnews.com/2020/05/14/gilead-should-ditch-remdesivir-and-focus-on-its-simpler-safer-ancestor/
GS-441524 is used by affluent cat owners to treat feline infectious peritonitis (FIP), a lethal coronavirus disease of cats. The drug has a ~96% cure rate.
https://www.theatlantic.com/science/archive/2020/05/remdesivir-cats/611341/
It is available from grey-market Chinese suppliers and resellers for a few thousand dollars.
https://www.theatlantic.com/science/archive/2020/05/remdesivir-cats/611341/
It is available from grey-market Chinese suppliers and resellers for a few thousand dollars.
Developing countries subject to convoluted legal and chemical constraints to license and produce remdesivir should strongly consider GS-441524 instead.
The original patent is from 2009, vs. 2017 for remdesivir. Some jurisdictions may already authorize open generic production.
The original patent is from 2009, vs. 2017 for remdesivir. Some jurisdictions may already authorize open generic production.
There is also a second drug commonly used in contemporary FIP treatment, GC376, a coronavirus protease inhibitor. https://journals.sagepub.com/doi/full/10.1177/1098612X17729626
GC376 is effective in vitro against SARS family coronaviruses as well.
It also has rather low toxicity.
It is currently being pursued for repurposing into human use, for the treatment of COVID-19. https://www.ptcommunity.com/wire/anivive-repurposes-veterinary-drug-gc376-covid-19-and-submits-pre-ind-fda
It also has rather low toxicity.
It is currently being pursued for repurposing into human use, for the treatment of COVID-19. https://www.ptcommunity.com/wire/anivive-repurposes-veterinary-drug-gc376-covid-19-and-submits-pre-ind-fda
GS-441524 is essentially equivalent to remdesivir, and is a nucleotide analogue and inhibitor of viral RNA polymerase-- the same class as e.g. favipiravir, EIDD-2801, galidesivir, etc.
GC376 is a viral protease inhibitor, the same class as nelfinavir, atazanavir, lopinavir, etc.
GC376 is a viral protease inhibitor, the same class as nelfinavir, atazanavir, lopinavir, etc.
Also, here is the synthesis scheme for GS-441524 and close relatives:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126871/pdf/main.pdf
It is indeed substantially nicer than the one for remdesivir.
Overall yield ex. mechanical losses should be slightly under 20% (vs. 0.3% for remdesivir).
https://twitter.com/__ice9/status/1252352284215787526?s=20
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126871/pdf/main.pdf
It is indeed substantially nicer than the one for remdesivir.
Overall yield ex. mechanical losses should be slightly under 20% (vs. 0.3% for remdesivir).
https://twitter.com/__ice9/status/1252352284215787526?s=20
GS-441524 is compound 3a in the paper linked above.
There is an unconfirmed rumor that Gilead was making remdesivir from Chinese-produced GS-441524, and may have cancelled as much as several metric tons of orders on middling trial results, causing a surplus of GS-441524 inventory in China. Alibaba sellers should have more color.
Adding Yan and Muller preprint expounding further from the general audience press article at the top of this thread: https://twitter.com/victoriacyanide/status/1267961727649484801?s=20
