5 ms·
True but both are prodrugs and GS-441524 is downstream on the metabolic chain from Remdesivir.
by fspeech 6y ago
True but both are prodrugs and GS-441524 is downstream on the metabolic chain from Remdesivir.
- lend000 6y agoInteresting, do you have a source? So you're saying you get a dose of GS-441524 regardless as Remdesivir decays?
- s1artibartfast 6y agoYes, this was a central point addressed in the article
- ggm 6y agoIts "upstream" in terms of being a 3 step drug not a 5 step drug and more of the active principle enters the bloodstream. So if we are in operations research linear programming mode, it may be less efficacious in some ways but its simpler to make and more of the active principle is liberated into the body. Would you rather have more drug to use on more people with more of it in the body, or a better drug but in shorter supply which needs a higher dose?
- s1artibartfast 6y agoYes, this was a central point addressed in the article
- labawi 6y agoI understood the article as: most remdesivir is converted to GS, hence most of the effects should presumably be from GS. That would give a good chance of being actually upstream for most relevant purposes. > In multiple studies testing remdesivir in coronavirus-infected mice or rhesus macaques, it was rapidly converted to GS-441524 in the bloodstream.
- ggm 6y agoI think you need to re-read the whole article. Literally the next paragraph explains something relevant. Take the latest controlled study conducted in rhesus macaques infected with SARS-CoV-2: After remdesivir was administered intravenously, GS-441524 was present in serum samples at concentrations 1,000-fold greater than remdesivir. Upon completion of the study, the researchers found that only GS-441524 — not remdesivir — was detected in the macaques’ lungs, yet they exhibited no signs of respiratory disease, significantly reduced viral loads, and a distinct reduction in damage to lung tissue. Such results reinforce those obtained from a prior study, also in macaques, and data from other species that GS-441524 exhibits strong antiviral activity. The active agent in the bloodstream from both drugs is GS-441524 triphosphate. The 3-step pro-drug GS-441524 releases more into the bloodstream than remdesivir. remdesivir takes 5 steps to make. GS-441524 takes 3 steps. Upstream means closer to the source. Something which takes 3 steps is upstream of something which takes 5 steps, because it is closer to the source. You have completely inverted the sense of the article. Remdesivir is downstream (5 not 3 steps) of GS-441524 and remdesivir releases less not more of the triphosphate.
- labawi 6y agoSo .. you go through GS to make remdesivir and it then goes through GS to be activated? (I thought you were disputing this point) If so, then in what way is remdesivir better?
- lend000 6y agoI've been exposed as someone who comments on links he hasn't read.