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Viral Mutations00:36

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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Updated: Nov 2, 2025

Indel Detection following CRISPR/Cas9 Mutagenesis using High-resolution Melt Analysis in the Mosquito Aedes aegypti
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Decoding molnupiravir-induced mutagenesis in SARS-CoV-2.

Luis Menéndez-Arias1

  • 1Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid, Madrid, Spain.

The Journal of Biological Chemistry
|June 12, 2021
PubMed
Summary

Molnupiravir, an investigational COVID-19 therapy, introduces errors into viral RNA replication. This mechanism, involving the nucleoside analog β-D-N4-hydroxycytidine (NHC), can lead to viral error catastrophe.

Keywords:
COVID-19RNA polymeraseSARS-CoV-2antiviral druglethal mutagenesismolnupiravir

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Area of Science:

  • Biochemistry
  • Virology
  • Drug Development

Background:

  • Molnupiravir is an investigational antiviral drug for COVID-19.
  • The precise biochemical mechanisms of molnupiravir-induced mutagenesis were previously unexplored.
  • Understanding these mechanisms is crucial for evaluating drug efficacy and safety.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which molnupiravir induces mutagenesis in SARS-CoV-2.
  • To investigate the role of the nucleoside derivative β-D-N4-hydroxycytidine (NHC) in viral RNA replication and mutation.

Main Methods:

  • Incorporation of NHC into viral RNA.
  • Analysis of RNA-dependent RNA synthesis using NHC as a template.
  • Modeling of mutagenesis pathways.

Main Results:

  • NHC is incorporated into the SARS-CoV-2 genome during RNA replication.
  • Incorporated NHC is recognized as a template, leading to errors during subsequent RNA synthesis.
  • A model for molnupiravir-induced mutagenesis consistent with virological data was proposed.

Conclusions:

  • Molnupiravir's therapeutic effect is linked to its ability to induce extensive viral mutations.
  • The drug drives SARS-CoV-2 towards an "error catastrophe," potentially inhibiting viral replication.
  • This study provides critical insights into the biochemical basis of molnupiravir's antiviral action.