New alternative to Paxlovid seems to prevent Long Covid in mice

Posted by sanDGuy @sandguy, May 20 3:34pm

"A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID"
https://www.nature.com/articles/s41467-025-57905-4
(published April 3)

Reading the above study made my eyes AND brain hurt, as a layperson, but the gist of it seems to be that while Paxlovid targets the essential CoV main protease (Mpro), an enzyme required to cleave viral polypeptides into functional proteins, these researchers have found a compound, WEHI-P8, that instead target PLpro, a further essential coronaviral protease.
This was conducted on mice, and they found that in addition to improved recovery from the acute phase compared to Paxlovid, it offered significant resistance to Long Covid, which the paper stated Paxlovid fails to do.
They dissected lungs to see this improved response, plus somehow measured brain functionality, if I understood correctly.
Of course, this doesn't NECESSARILY translate to better outcomes in humans, but is promising as a possible PREVENTATIVE (not a cure) for LC.
In any case, we should all be thankful to the poor, little "meeses" for their service in sacrificing their lives for Humanity, .

Interested in more discussions like this? Go to the Post-COVID Recovery & COVID-19 Support Group.

roadog66 | @roadog66 | May 21 8:04am

Well this is certainly good news for mice. The problem for humans is that humans aren't taking packs loaded so why are they going to take this? Most people don't think about long covid. We need a cure for when they do but this is certainly in advance of knowledge. Sorry for the errors in this dictated message.

bmekdeci | @bmekdeci | May 23 11:53am

I took Paxlovid after my first bout with Covid in 2022. It is a dreadful medication that makes your mouth taste like a garbage can. It did not prevent Covid-related heart problems, high blood pressure and hearing loss which happened about a month after I tested negative for Covid.

The next time I got Covid a few months later, I declined to take Paxlovid again. This time I took
Lagevrio (molnupiravir). It worked much better and I didn't have any extra problems.

Lagevrio (molnupiravir) actually came on the market before Paxlovid and I can only guess more aggressive marketing gave Paxlovid the edge.

sanDGuy | @sandguy | May 25 1:02pm

In reply to @bmekdeci "I took Paxlovid after my first bout with Covid in 2022. It is a dreadful medication..." + (show)

That's interesting about molnupiravir! I looked it up, and as you say, it definitely is an alternative to Paxlovid.
And "Garbage Can Mouth" sounds rather off-putting!
If I catch Covid for the second time (and I just got, like, my eighth booster), I think I will get my doctor to prescribe it.
Plus, apparently, there is such a thing as "Paxlovid rebound", although perhaps this might happen with molnupiravir, too.
(God, there are so many variables at play with this illness, aren't there?)
But thanks very much for that info!

sanDGuy | @sandguy | Jun 5 7:29pm

In reply to @roadog66 "Well this is certainly good news for mice. The problem for humans is that humans aren't..." + (show)

OMG re-read this and finally "unpacked" your "pack loaded" term! LOL.
Phonics, PHONICS!
As a matter of fact, many people who have pre-existing conditions (e.g. lung problems) or other susceptibilities are indeed recommended to be prescribed Paxlovid during the acute phase (MUST be done then) of Covid.

I think that, given my age (and LC), I would indeed try to get the similar anti-viral Lagevrio, prescribed instead, though, as bmekdeci suggested.

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