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We Made One Gram Of Remdesivir

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Re: We Made One Gram Of Remdesivir

#231

Post by ashildr »

DrAwdeOccarim wrote: post #95
ashildr wrote: post #74

Earlier quoted context omitted.

This mode of action is fascinating, some HIV medications work in a similar way. What I’m curious about is why this huge group attached to the adenosine-like group is needed. It seems to be rather complex for being a shoe to be thrown into cellular gear. Do you have an idea or pointer into the mode of action of this group?

I'm not familiar with the synthesis development of remdesivir, but typically those side groups are discovered through a process called Structure Activity Relationship (SAR). The basic idea is you start with a bunch of different compounds (like 1000's) and look at their ability to interfere with a specific enzyme in a high-throughput screen. When you rank the 1000's of compounds, some will work better than others. The…

Thanks, I’ll have some reading to do on easter, now :-)

Re: We Made One Gram Of Remdesivir

#232

Post by ashildr »

HarryHirsch wrote: post #163
ashildr wrote: post #74

Earlier quoted context omitted.

This mode of action is fascinating, some HIV medications work in a similar way. What I’m curious about is why this huge group attached to the adenosine-like group is needed. It seems to be rather complex for being a shoe to be thrown into cellular gear. Do you have an idea or pointer into the mode of action of this group?

The observation is correct. Remsedivir is a prodrug, the active compound looks like adenosine monophosphate. But that molecule bears too much charge to be able to cross cell membranes. Consequently medicinal chemists put protecting groups on the offending atom, to help the compound get out of the bloodstream and into cells. Once inside, those are cleaved off through nonspecific esterases and the molecule can't get ba…

Thanks for the good explanation of how Remdesivir enters a cell and stays there.

Re: We Made One Gram Of Remdesivir

#233

Post by ashildr »

ImaCake wrote: post #121
ashildr wrote: post #74

Earlier quoted context omitted.

This mode of action is fascinating, some HIV medications work in a similar way. What I’m curious about is why this huge group attached to the adenosine-like group is needed. It seems to be rather complex for being a shoe to be thrown into cellular gear. Do you have an idea or pointer into the mode of action of this group?

So looking at the wiki page image of Remdesivir [1] I can see that this looks a lot like the sugar-phosphate backbone that is integral to DNA and RNA. If you imagine DNA as a curling ladder, the nucleoside (adenosine) is the steps, and the sugar-phosphate pairs make up the rails on either side of the steps. The adenosine bit is attached to a five carbon sugar (pentagon with O at top) which is identical to the sugar i…

It does, thank you!

Re: We Made One Gram Of Remdesivir

#234

Post by ngngngng »

Symbiote wrote: post #126
ngngngng wrote: post #36

I've never learned a bit of Chemistry. I assume there are formulas to determine how substrates and reagents will react with each other? And the process chemists understand these formulas better than most? Apologies for the assumptions in these question, but are there many reactions in organic chemistry that are completely unknown? This actually seems pretty fun. I'd love to have a reason to study it and a means to do…

Which country's education system doesn't have any chemistry at all? Chemical formulae are required study for 11-14 year olds in England, for what it's worth. (Probably starting with words: methane + oxygen → carbon dioxide, and later writing a balanced equation: CH₄ + 2O₂ → CO₂ + 2H₂O.) The reaction presented is obviously much, much more complicated, but the same concept. Edit: catalysts are covered too, although I d…

This was in California. I had to take a science class but there were many options and I just took other things besides chemistry.

Re: We Made One Gram Of Remdesivir

#235

Post by Isinlor »

aaai wrote: post #221
nitrogen wrote: post #195

Earlier quoted context omitted.

I know Wikipedia has evolved considerably from its original intent, but isn't one of the quintessential goals of an encyclopedia to have an approachable summary of every topic?

"Approachable" means that it might require some effort from the reader (eg. in worst case scenario, a reader not familiar at all with the domain would have to look up the definition of every word in a sentence and do that recursively a few steps, until he/she gets some domain familiarity by reading the equivalent of a few hundreds pages or less), but you can approach it, and in exchange it gives precise and rich info…

I've done undergrad level mathematics and a lot of Wikipedia articles about mathematics is complete gibberish to me even if I put a lot of effort (hours) in understanding them. My estimate would be that more than 99% of population would not be able to gain anything from reading them.

Re: We Made One Gram Of Remdesivir

#236

Post by kohtatsu »

aaai wrote: post #220
koboll wrote: post #161

Earlier quoted context omitted.

This is such a great description. Compare how Wikipedia describes the same process [ https://en.wikipedia.org/wiki/Adenosine#Research ]: > The adenosine analog NITD008 has been reported to directly inhibit the recombinant RNA-dependent RNA polymerase of the dengue virus by terminating its RNA chain synthesis. This interaction suppresses peak viremia and rise in cytokines and prevents lethality in infected animals, ra…

May be hard to understand for ppl. with no background, but that description includes the crucial bit of information that OPs "easy to grok" simplified description lacks: > inhibit the [...] RNA polymerase of the [..] virus If it would just simply stop RNA synthesis (eg. inhibit any RNA-polymerase) or if it would actually break RNA in general , it would kill HUMANS just as well! The point of antiviral compounds is to…

I noticed that hand waving in the OP too.

Any insight on how it manages not to harm non-virus stuff?

(Not a biologist. Also you're using a lot of italics and it harms the readability at least for me.)

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