Thread by @michaelzlin

Today in Science, two prominent viral drug experts express concerns about molnupiravir, Merck's mutagenic COVID pill:
1. Mutating patient DNA not ruled out
2. Mutating viral genomes for sure, risk unknown

Common theme: We're gambling when using this drug

science.org/doi/10.1126/sc…

Raymond Schinazi is a well known antiviral drug developer, called the "King of the Pills". His wikipedia page lists the many marketed HIV and HCV drugs he has developed based on nucleoside analogues like molnupiravir.
science.org/doi/10.1126/sc…

In fact Schinazi is the one person who has the most knowledge of molnupiravir (MOV). He's been studying its active metabolite NHC as an antiviral since 2003 (PMID 12499198). He didn't push it to clinic because of mutagenesis concerns. That comes out clearly above, but also below

Regarding molnupiravir accelerating mutagenesis of the viral gene pool, the article points out immunocompromised patients who don't clear the virus quickly could be breeding mutated but viable viruses, and that the risk of immunoevasive variant generation is unknown. I agree.

Doing something with unknown but nonzero probability of dire consequences is the definition of an irresponsible gamble. Every government that has approved molnupiravir and allowed its distribution (US, UK, India, Mexico, etc) is taking that gamble without public consent.

And MOV is only 30% effective, compared to ~90% for mAbs or the other oral drug, Paxlovid. So how did this possibly get approved? I've spoken with the authors but will keep our conversation confidential. However you can read what Schinazi himself wrote, after he tweeted my op-ed:

For those not used to academic speak, this essay is as critical an assessment of a FDA decision that you will ever read. It's brave of the authors to write this. One is even writing against his own declared interests. Silence is always easier in academia.