A significant class of antiviral medications includes nucleoside analogs. Molnupiravir is one such drug, which works by causing the virus to mutate more frequently, which can be fatal. However, their ability to cause mutations could raise questions about their evolutionary safety.
A research team that includes Martin Nowak, Harvard professor of mathematics and biology, took a math-based dive into whether molnupiravir could lead to harmful mutations of the virus that causes COVID-19. Scientists developed a mathematical framework to estimate the total mutant load produced with and without mutagenic treatment.
Potentially encouraging news is offered as they draw close: Molnupiravir seems “marginally evolutionarily safe.” In other words, when appropriately administered, the medication reduces the virus’s capacity to produce mutants that survive.
The model compares the total number of original and mutant viruses produced by an individual during infection and represents the rise and fall of viral load following infection. They discovered that a patient receiving the medication makes fewer mutants over time than a patient taking a placebo.
When molnupiravir is used, the virus’s “error threshold,” or the point at which mutations make it difficult for the virus to survive, is triggered. Death by mutation is called lethal mutagenesis.
Nowak said, “We propose that, in the future, these types of drugs should be pursued, and their evolutionary safety should be carefully evaluated. Molnupiravir belongs to a class of drugs called nucleoside analogs, which include drugs that treat HIV.”
According to the researchers, a medicine with even more potential for deadly mutagenesis might be more evolutionary safer than molnupiravir at the moment.
Additionally, according to their research, molnupiravir seems more efficient for people with trouble independently eliminating the virus. Giving it to folks who can swiftly clear the virus might be less evolutionary safe. However, the overall number of mutations remains low in those healthier people.
Nowak said, “We estimate that Molnupiravir is narrowly evolutionarily safe, subject to the current estimate of parameters. Evolutionary safety can be improved by restricting this drug to individuals with a low immunological clearance rate and, in the future, by designing treatments that lead to a greater increase in mutation rate.”
Journal Reference:
- Lobinska G, Pilpel Y, Nowak MA (2023) Evolutionary safety of lethal mutagenesis driven by antiviral treatment. PLoS Biol 21(8): e3002214. DOI: 10.1371/journal.pbio.3002214