Nature: A Molnupiravir-Associated Mutational Signature in Global SARS-CoV-2 Genomes

 

#17,694

One of the realities of life is that anything you do - or fail to do - can change the course of history. Every day, and in a thousand ways, we all make decisions large and small that change the future.  Most are trade offs, based on perceived risks and rewards.  

Sometimes we get it right, sometimes we get it wrong. And sometimes, there's simply no way of knowing which is the right choice.  Even in hindsight. 

Yesterday the Journal Nature published a study which finds unique mutation signatures in SARS-CoV-2 genomes in countries where the antiviral molnupiravir ( LAGEVRIO) has been widely prescribed.  This study first appeared as a preprint on the medRxiv server last month. 

 

Molnupiravir works by forcing the virus to generate random (usually deleterious or neutral) mutations during replication, which in turn reduces viral fitness, and ultimately viral load.

 

This study found some evidence of onward transmission of molnupiravir-derived lineages, although there is no evidence that these mutations have led to more dangerous variants.  This highly technical study is behind a paywall, but for those without access, the preprint remains available. 

Article

Published: 25 September 2023

A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes

Theo Sanderson, Ryan Hisner, I’ah Donovan-Banfield, Hassan Hartman, Alessandra Løchen,

Thomas P. Peacock & Christopher Ruis

While this study indicates that molnupiravir use does influence SARS-CoV-2's evolution - and raises some important questions about this drug's mechanism of action -  its impact on public health or the direction of the pandemic are far less apparent.    

Theo Sanderson, the lead author of this study, published a long thread on Twitter/X yesterday (excerpts below) which describes this study far better than I could.  It is well worth reading in its entirety. 

Predictably, a lot of people on social media are demonizing molnupiravir, even though there are far more questions than answers at this point.  

While it may not exonerate the drug, it is worth noting that COVID's Alpha, Delta, and Omicron lineages all emerged before the approval of Molnupiravir (in late 2021- early 2022), and thus far, no VOCs (Variants of Concern) have been linked to molnupiravir-associated mutations.

Admittedly, that could change. Which is why the authors call for ". . .  continued investigations into the effects of molnupiravir in viral sequences, and the transmissibility of molnupiravir-derived lineages."