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Fun fact: #remdesivir is almost certainly not the species that reaches #COVID19 patients' lungs! Its nucleoside #GS441524 is. Wrote this piece for @statnews explaining this! @GileadSciences consider aerosolizing GS-441524 prophylaxis. Pls read and RT! 1/x
I've been reading a lot of general audience/science articles on #remdesivir. Many of these articles seem to confuse nucleoSIDES with nucleoTIDES. Here's the difference, feat. important figures. 2/x
#remdesivir is a nucleoTIDE monophosphate analogue. #GS441524 is a nucleoSIDE analogue. 3/x
WHY IT MATTERS: Almost no attention has been given to the antiviral activity of the nucleoside, GS-441524, even though multiple in vivo studies have shown that it is the DOMINANT SPECIES found in the lungs of coronavirus-infected animal models. 4/x
HOW IS THIS POSSIBLE? #remdesivir is a pro-drug. It must undergo bioactivation steps to the active triphosphate inhibitor. Most steps are supposed to occur inside the cell, but some steps can happen outside. One of these steps inadvertently releases #GS441524. 5/x
WHAT ABOUT IN VITRO DATA? Some data show #remdesivir > #GS441524 in potency. But the most important in vitro study in primary human airway epithelial cells show no stat. sig. difference b/w the 2. Minor differences don't matter if only GS-441524 is in the lungs in vivo. 6/x
SO WHY IS THIS IMPORTANT AGAIN? Well, #remdesivir is kinda hard to synthesize! #GS441524 is not. What's the point of laboring to make Remdesivir when GS-441524 is the one that reaches the lungs? GS-441524 is also low MW/hydrophilic, making aerosolization for prophylaxis easier.
Key article by Pedersen et al. JFMS 2019 showing the efficacy of #GS441524 in cats with feline coronavirus. It's a good read everyone. @ucdavisvetmed
Also, a well-written piece by @sarahzhang @TheAtlantic on the social backstory of #GS441524 when Pedersen was investigating its use in cats. 👏👏👏…
Hot off the press @NPR! #remdesivir distribution wouldn't be such a lottery if there was more of it.
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