Related Experiment Video

Updated: Jul 19, 2025

Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
18:10

Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency

Published on: June 16, 2011

29.6K

Evolutionary safety of lethal mutagenesis driven by antiviral treatment

Gabriela Lobinska1, Yitzhak Pilpel1, Martin A Nowak2

  • 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Plos Biology
|August 8, 2023
PubMed

Insights

Mutagenic antiviral drugs like Molnupiravir may raise evolutionary safety concerns. Mathematical modeling suggests Molnupiravir is narrowly safe, but optimizing treatment and drug design can enhance viral evolution safety.

Area of Science:

  • Virology
  • Evolutionary Biology
  • Computational Biology

Background:

  • Nucleoside analogs are key antiviral agents, with some inducing lethal mutagenesis in viruses.
  • The mutagenic potential of these drugs raises concerns about viral evolution and the generation of resistant mutants.
  • Evolutionary safety is defined as the probabilistic assurance that treatment does not increase the number of viable viral mutants.

Purpose of the Study:

  • To develop a mathematical framework for estimating viral mutant load with and without mutagenic treatments.
  • To assess the evolutionary safety of Molnupiravir, an FDA-approved COVID-19 treatment.
  • To identify factors influencing the rate of viral mutant appearance and propose strategies for improving evolutionary safety.

Main Methods:

  • A mathematical framework was developed to estimate total mutant load.
  • Predictions were made regarding mutant appearance rates based on treatment timing and patient immune competence.
  • The framework was applied to Molnupiravir, using realistic assumptions about viral genome vulnerability and mutant viability.

Main Results:

  • Molnupiravir is estimated to be narrowly evolutionarily safe under current parameter estimates.
  • Treatment timing and patient immune competence significantly influence the rate of mutant appearance.
  • Restricting Molnupiravir use to individuals with lower immune clearance rates can improve evolutionary safety.

Conclusions:

  • Molnupiravir's evolutionary safety is marginal, highlighting the need for careful consideration of its use.
  • Future antiviral drug development should aim for a greater increase in mutation rate to ensure evolutionary safety.
  • A mathematical rule was derived to guide the design of treatments for enhanced evolutionary safety across various pathogens.

More Related Videos

A Simple and Efficient Approach to Construct Mutant Vaccinia Virus Vectors09:16

A Simple and Efficient Approach to Construct Mutant Vaccinia Virus Vectors

Published on: October 30, 2016

11.3K
Engineering and Evolution of Synthetic Adeno-Associated Virus AAV Gene Therapy Vectors via DNA Family Shuffling21:55

Engineering and Evolution of Synthetic Adeno-Associated Virus AAV Gene Therapy Vectors via DNA Family Shuffling

Published on: April 2, 2012

28.6K

Related Concept Videos

Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.4K
Mutations in Microorganisms01:18

Mutations in Microorganisms

Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
32
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.2K
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
14.0K
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K