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We Made One Gram Of Remdesivir

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Re: We Made One Gram Of Remdesivir

#61

Post by heurifk »

kccqzy wrote: post #22

Remdesivir is an analog of adenosine, one of the four building blocks of RNA. Just look at the main structure and you'll agree they look similar. It turns out the mechanism of action of this drug is that it's supposed to be confused with adenosine, so that the viral RNA replication process uses remdesivir instead of adenosine, which later breaks the RNA†. Our body, or really, all biological processes can synthesize i…

Normal cells also use RNA during protein synthesis. Why doesn't remdesivir disrupt that too and kills healthy cells?

Re: We Made One Gram Of Remdesivir

#62

Post by ggm »

HarryHirsch wrote: post #17
ggm wrote: post #13

Earlier quoted context omitted.

At seven hundred freaking degrees, fluorine starts to dissociate into monoatomic radicals, thereby losing its gentle and forgiving nature. Gentle and Forgiving nature...

The inimitable Martin Poliakoff demonstrates it here: https://www.youtube.com/watch?v=vtWp45Eewtw

Great communication

Re: We Made One Gram Of Remdesivir

#63

Post by TomVDB »

samcheng wrote: post #9
ebg13 wrote: post #3

The writing is so good, I had to double check that it wasn't written by Derek Lowe.

Here's his most famous article on FOOF (Dioxygen Diflouride) https://blogs.sciencemag.org/pipeline/archives/2010/02/23/th... It seems there are multiple chemist-author hybrids out there!

Like the story about the SR-71 Blackbird asking for a speed check, I will never not read the FOOF article again when somebody posts the link.

(https://tribunist.com/technology/sr-71-blackbird-pilot-troll...)

Re: We Made One Gram Of Remdesivir

#64

Post by joshvm »

djaque wrote: post #49
Vaslo wrote: post #34

In my former life I was a graduate organic chemist, but I “quit” with a Masters. I loved Synthetic Chemistry as an undergrad and thought I wanted a PhD in. There were three lousy things (for me) about the career that made me bail. 1). So many syntheses have horrible yields just like this one. You’d start with grams of material to end up with micrograms. I loved solving these problems as an undergrad in books, but rea…

That's kind of my experience with research, but in physics. Already have three projects under my belt w/ no publishable results. All of them involved much more work than the other grad. students in my lab including building like three different instruments from scratch, but the other students have published. Their projects were much more "safe" than mine and their papers are pretty small, but at least they have paper…

Don't worry. Instrumentation is a pain for publishing because often it creeps into engineering territory. I spent a year of my PhD trying to get something to work, it didn't and I ended up building an entirely new instrument in the third year. That's how it goes. I know people who came out of their PhDs with five papers (in the UK that's a big deal), but they're in fields where its relatively easy to publish and/or got lucky with their topic. Or you work with someone with a funky new dataset that breeds publications.

I think most instrumentation scientists are sympathetic to this. There are also lots of instrumentation jobs that don't require stupid numbers of publications because it's not practical to find candidates. There are relatively few good hardware people in the sciences (especially fields where you can't get a mech/electrical engineer).

I suggest finding some conferences to start. They're a good venue for telling people what you did. There are also journals specifically for building stuff, SPIE has a lot for astrophysics, for example.

Re: We Made One Gram Of Remdesivir

#65

Post by disillusioned »

girvo wrote: post #50
Vaslo wrote: post #34

In my former life I was a graduate organic chemist, but I “quit” with a Masters. I loved Synthetic Chemistry as an undergrad and thought I wanted a PhD in. There were three lousy things (for me) about the career that made me bail. 1). So many syntheses have horrible yields just like this one. You’d start with grams of material to end up with micrograms. I loved solving these problems as an undergrad in books, but rea…

> So many failures could be logged so I didn’t waste my time doing non-working or poor yielding reactions In a different but related world, clandestine chemists share failures more often than they do their successes, at least in the communities I was a part of a very long time ago. I'd wager this is because our substrates, reagents and solvents are such a pain in the arse to get compared to an actual lab, that wastin…

Do they then go on to be script consultants for Breaking Bad?

Re: We Made One Gram Of Remdesivir

#66

Post by est31 »

heurifk wrote: post #61
kccqzy wrote: post #22

Remdesivir is an analog of adenosine, one of the four building blocks of RNA. Just look at the main structure and you'll agree they look similar. It turns out the mechanism of action of this drug is that it's supposed to be confused with adenosine, so that the viral RNA replication process uses remdesivir instead of adenosine, which later breaks the RNA†. Our body, or really, all biological processes can synthesize i…

Normal cells also use RNA during protein synthesis. Why doesn't remdesivir disrupt that too and kills healthy cells?

There is no RNA cloning machinery in our cells. The RNA is instead copied from the DNA in the nucleus. Viruses like the coronavirus actually bring their own RNA cloning machinery that's assembled by the cell. Remdesivir only blocks the RNA cloning proteins of the virus.

Re: We Made One Gram Of Remdesivir

#67

Post by est31 »

> Here are the real numbers for the reactions in Scheme 1: 0.25 x 0.58 x 0.74 x 0.21 x 0.23 = .005 (0.5%)

This reminds me of the problems to scale up EUV lithography which are bottlenecked on producing strong enough EUV light. They put in 20 kW of power to get out 200 W at the target wavelength of 13.5 nm, so light generation itself only has 1% efficiency, and then you need to reflect it at mirrors etc. to focus it (lenses don't work at those wavelength) and that makes only 2% of the light actually reach the waver [2].

[1]: https://www.laserfocusworld.com/blogs/article/16569161/the-s...

[2]: https://en.wikipedia.org/wiki/Extreme_ultraviolet_lithograph...

Re: We Made One Gram Of Remdesivir

#68

Post by rocqua »

est31 wrote: post #66
heurifk wrote: post #61

Earlier quoted context omitted.

Normal cells also use RNA during protein synthesis. Why doesn't remdesivir disrupt that too and kills healthy cells?

There is no RNA cloning machinery in our cells. The RNA is instead copied from the DNA in the nucleus. Viruses like the coronavirus actually bring their own RNA cloning machinery that's assembled by the cell. Remdesivir only blocks the RNA cloning proteins of the virus.

Doesn't that mean that Remdesivir would essentially defeat _all_ RNA viruses? Or is the effectiveness dependent on the exact RNA cloning mechanism used by the virus?

Re: We Made One Gram Of Remdesivir

#69

Post by nython »

Vaslo wrote: post #34

In my former life I was a graduate organic chemist, but I “quit” with a Masters. I loved Synthetic Chemistry as an undergrad and thought I wanted a PhD in. There were three lousy things (for me) about the career that made me bail. 1). So many syntheses have horrible yields just like this one. You’d start with grams of material to end up with micrograms. I loved solving these problems as an undergrad in books, but rea…

> There were happy go lucky chemists that fell into projects that were smooth as butter

If it makes you feel any better (I 'quit' at the start of my bioinformatics PhD), there's a high chance that their projects went smooth as butter because they were also happy-go-lucky about double-checking their results. See for example that 75% yield paper you mentioned.

Re: We Made One Gram Of Remdesivir

#70

Post by dguest »

Vaslo wrote: post #34

In my former life I was a graduate organic chemist, but I “quit” with a Masters. I loved Synthetic Chemistry as an undergrad and thought I wanted a PhD in. There were three lousy things (for me) about the career that made me bail. 1). So many syntheses have horrible yields just like this one. You’d start with grams of material to end up with micrograms. I loved solving these problems as an undergrad in books, but rea…

In point 3: did you try to contact the authors of the paper you were trying to reproduce?

I don't know organic chemistry, but in my field the authors are often willing to discuss their results, especially if it might mean more citations for them.

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