Thread by @michaelzlin

ICYMI: Another reason not to take #molnupiravir is mutagenesis of the patient DNA hasn't been ruled out.

We've already ruled *in* viral mutagenesis.

The push to approve molnupiravir feels like Challenger-style "go fever".

Sanity needs to prevail.

nytimes.com/2021/12/13/hea…

When we discovered boceprevir has activity against SARSCoV2, we contacted Merck and let them know, because it was their drug and we figured they could modify the compound for even better activity.

Boceprevir activity below, also published by others.
biorxiv.org/content/10.110…

Well Merck didn't pursue a boceprevir derivative for COVID19, and chose instead to bet on a new drug that creates mutations in the virus as its only mechanism of action. This had never been tried before (there's a belief ribavirin does, but it has other inhibitory effects).

Instead Pfizer took the boceprevir ball and ran with it. Though they won't say so, that's where PF-07321332 (Paxlovid) came from. Just look at the structures.

(Paxlovid is often misreported as coming from Pfizer's SARS1 inhibitor libraries, confusing PF-07321332 for PF-0083521)

So Pfizer did what Merck should have done: modify boceprevir for SARSCoV2. (We're doing the same but as we don't have the $billions of Pfizer, our drugs may be a bit slower to come out.)

Meanwhile Merck is doing what nobody should be doing: playing with mutagens.

And Pfizer of course made the correct choice for the patients too: 89% efficacy in preventing hospitalization vs 30%, with no risk of mutating your DNA or creating deadlier or more contagious viral variants.

So for those thinking I'm unfair to Merck: We told Merck, and they confirmed they knew, of boceprevir's promise in early 2020. They had as much ability as Pfizer to make Paxlovid or something like it, and they chose not to.

For technical details, you can read my earlier thread on sublethal viral mutagenesis. Only a matter of time before someone taking molnupiravir coughs on someone before finishing the 40-pill course (or after stopping treatment early upon "feeling better")

https://twitter.com/michaelzlin/status/1464366708156731395