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All Studies   All Outcomes    Recent:   

Treating a Pandemic Respiratory Disease with a Mutagen is a Doomsday Scenario

Dec 2021  
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Review of molnupiravir's mutagenic mechanism of action, and analysis of the increased probability of creating dangerous variants.
Reviews covering molnupiravir for COVID-19 include Anonymous, Bacigalupo, Goldstein, Hadj Hassine, Kosakovsky Pond, Malone, Swanstrom, Waters.
Anonymous et al., 3 Dec 2021, preprint, 1 author.
This PaperMolnupiravirAll
Treating a Pandemic Respiratory Disease with a Mutagen is a Doomsday Scenario
Merck's Molnupiravir is a global catastrophic risk. Its broad use as a treatment for COVID-19 will create dangerous variants of SARS-COV-2. It is already in use in some countries. Molnupiravir ("MOLN"), a presumed anti-COVID19 drug, acts by significantly increasing the RNA error rate in the coronavirus replication. That exponentially increases the probability of many mutations in a single copy. Copies containing a large set of new mutations are disproportionately likely to create dangerous mutations. Patients taking MOLN are expected to carry and shed the virus in almost equal volumes as untreated patients. Estimates show that MOLN would increase the frequency of sets of 8 mutations by 3,000 times, and sets of 12 mutations by 240,000 times, per virus generation, per person. This does not include recombinations and many other effects which are likely to compound these results. Multiple rounds of replication and natural selection per person further increase the threat. The impact cannot be detected immediately due to a possible lag between the appearance of a new variant and the necessary changes in external conditions, which lead to its spread. At least some of the many artificial variants, induced by the MOLN treatment, are likely to combine immune escape, higher contagiousness, and higher virulence, just to mention a few. This would be a gain-of-function experiment, performed on the entire human race.
References
Bull, Joyce, Gladstone, Molineux, Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis, Genetics, doi:10.1534/genetics.113.154195
Cder Brief2, Phase II/III
Drummond, Why High-error-rate Random Mutagenesis Libraries are Enriched in Functional and Improved Proteins -ScienceDirect
Gordon, Tchesnokov, Schinazi, Götte, Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template, J Biol Chem
Ismagilov, Regulations, None
Merck, Molnupiravir, None
Nelson, Otto, Mutagenic antivirals: the evolutionary risk of low doses -SARS-CoV-2 coronavirus Virological
Zhou, Hill, Sarkar, Tse, Woodburn et al., β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, J Infect Dis, doi:10.1093/infdis/jiab247
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