Intended for healthcare professionals

Rapid response to:


Covid-19: Molnupiravir reduces risk of hospital admission or death by 50% in patients at risk, MSD reports

BMJ 2021; 375 doi: (Published 04 October 2021) Cite this as: BMJ 2021;375:n2422

Read our latest coverage of the coronavirus pandemic

Rapid Response:

Molnupiravir is mutagenic for mammals too

Dear Editor

Although the Ingelfinger rule seems to have dissolved into dust with the coming of COVID-19,[1] I was a little disappointed that your Journal appears to have mirrored Merck's press release concerning molnupiravir without substantial critical markup.

It is clear that molnupiravir induces intense mutagenesis in SARS-CoV-2, [2] and it is this that accounts for its efficacy.

It may be worthwhile noting the evidence that β-d-N4-hydroxycytidine, the active metabolite of molnupiravir, is not only cytotoxic but also mutagenic in mammalian cells.[3] The drug may damage DNA.

There is a certain irony that vaccine-shy individuals who have believed the untruth that vaccines against SARS-CoV-2 alter DNA, seem poised to reach for a perceived 'alternative' that may indeed alter their DNA adversely. This worry is borne out by the rise in the Merck share price and Moderna's corresponding drop, as reported by Reuters.[4]

Buyer beware.


[1] Badrinath P. Have we abandoned the Inglefinger rule in the COVID era? BMJ. 2020 Jun 9;369:m2279. URL:

[2] Kabinger F, Stiller C, Schmitzová J, Dienemann C, Kokic G, Hillen HS, et al. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021 Sep;28(9):740-746. doi: 10.1038/s41594-021-00651-0

[3] Zhou S, Hill CS, Sarkar S, Tse LV, Woodburn BMD, Schinazi RF, et al. β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells. J Infect Dis. 2021 Aug 2;224(3):415-419. doi: 10.1093/infdis/jiab247

[4] Krauskopf L, Maddipatla M. Merck COVID-19 pill success slams Moderna shares, shakes up healthcare sector. URL:

Competing interests: No competing interests

09 October 2021
Johan M van Schalkwyk
Perioperative Physician
Auckland District Health Board
Auckland City Hospital, Auckland, NZ