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About Remdesivir

This is another installment of pharma related posts you guys will probably not read but I thought it was important enough to bring up.

Gilead pharmaceuticals presented findings from a limited study on severely ill Coronavirus patients using its anti-viral drug Remdesivir. The study shows that Remdesivir shows modest activity, reducing death rates by 62%. It’s not as impressive as it sounds but it’s not nuthin’.

For those of you who are mildly curious, this is the structure of Remdesivir:

Remdesivir’s modus operandi probably involves interfering with RNA in some way. Coronavirus is a retrovirus, meaning it only carries its RNA around with it for efficiency’s sake. It makes your cells do all the heavy lifting. The scaffold structure of this drug looks like a nucleotide (heterocycle A, sugar B, phosphate C). There are additional bits and pieces added to the scaffold that likely adds to its activity.

In regular non-Covid R&D, we would never do drug discovery this way. But this is an emergency. In regular time, we would identify a target protein of the virus and do high throughput screening (HTS) of a compound library against that target protein. The HTS would identify potential hits and the cheminformaticists and drug designers would mine bigger virtual compound libraries for compounds that look similar to it. Then we would go through a zillion iterations of optimizations with a project team with the biologists sucking up most of the meeting time talking about detergents and showing gels that are indistinguishable from last week’s gels. And all of that work is very important. I’m not trying to minimize it. But it does take a lot of time. It’s like everyone starting off blind and gradually seeing what they’re dealing with.

Ain’t nobody got time for that.

What we’ve done here is a little more direct. We’ve started with known anti-viral meds, given them to patients and seen if any of them helped. The good news is Remdesivir helps. The bad news is it’s like giving Tylenol to someone who has had major surgery. I mean, sure, it’s better than nothing but it’s not a cure. The activity of this type of drug needs to be optimized.

Would *I* take it if I had a severe case of Covid? Absolutely. I wouldn’t expect a miracle but it’s a hell of a lot better than hydroxychloroquine, which on top of being utterly ineffective is more likely to kill you. I’m putting that in my directives. Dexamethasone and Remdesivir, yes; hydroxychloroquine, no, non, Nyet

Anyway, back to the good news. Now that we know that this class of drugs works, we can mine the database directly and pass it on to medicinal chemists who will make slight modifications that can be tested in vitro (“in glass”, basically, a test that doesn’t require a live animal). If they look promising, they can be tested in vivo (in a live animal).

Will they give it straight to humans? Depends on what can be mined from the databases. If the mining shows up something that has already been tested for something else and has been found relatively non-toxic and easily available to the body, maybe? Well, hydroxychloroquine was hyped and fast tracked with less evidence so maybe. Otherwise, let’s just hope that med chem can crank out some compounds and get them tested.

So, get your hopes up but not too much over this announcement. I know that we are all breathlessly waiting for someone to announce a cure so things can get back to normal. That’s the way the media presents these things but the reality is much more realer. It’s going to take awhile.

In the meantime, cover your freakin’ face.

For more in-depth analysis on stuff like this, see Derek Lowe’s In The Pipeline blog.

11 Responses

  1. Way OT, but just had to reply to your Randy Rainbow blog post, in which you mentioned other Disney villains who could be part of his videos. You specifically mentioned Gaston. Voila!

    Please keep these science posts coming. You break down the details so clearly,

  2. I noticed a nitrile group in there (aka cyanide). I hope it doesn’t come loose! 😮

    The nitrogen linked to the phosphorus is the amino part of an alanine residue, esterified with a 2-ethyl-n-butyl group, if I read the molecule correctly.

    If I understand correctly, most non-corrosive poisons work the way this drug probably works on Corona-chan: the ion or molecule resembles something the organism’s biochemistry uses, closely enough that it works up to a point, but then fails. The late Isaac Asimov used the humble analogy of putting the wrong key into a lock, and jamming the lock.

    • OooOooo! Who are you anyway??

      • I thought I had mentioned here that I take a very amateur interest in chemistry. I own a few old chemistry texts, largely acquired from secondhand shops.

    • My point is to alert the user to the fact that there will be much hat but not much cattle about Remdesivir. In other words, don’t let your guard down. Yet.

  3. Off topic: Beaker Street Friday nights 9 PM – 12 AM Central time on
    arkansasrocks-dot-com (IIRC, TurdPress won’t let me post more than one link in a comment).

    Also, this week I found a site where you can listen to past editions of Beaker Street on MP3, if Friday night is an inconvenient time for you.


  4. I read it but I don’t really get it. Thanks anyway.

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