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Updated: Sep 26, 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

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Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity

Ikbel Hadj Hassine1, Manel Ben M'hadheb1, Luis Menéndez-Arias2

  • 1Unité de Recherche UR17ES30 "Génomique, Biotechnologie et Stratégies Antivirales", Institut Supérieur de Biotechnologie, Université de Monastir, Monastir 5000, Tunisia.

Viruses
|April 23, 2022
PubMed

Insights

Lethal mutagenesis uses mutagens to increase viral mutation rates, causing extinction. Drugs like molnupiravir show promise against RNA viruses but carry carcinogenic risks.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • RNA viruses have low mutation thresholds, making them vulnerable to increased mutation rates.
  • Lethal mutagenesis is a strategy to induce viral extinction by increasing mutation frequency.
  • Promutagenic nucleosides can experimentally trigger extinction events in viral populations.

Purpose of the Study:

  • To explore lethal mutagenesis as an antiviral strategy against RNA viruses.
  • To review the mechanisms and efficacy of nucleoside analogs in inducing viral extinction.
  • To assess the potential and limitations of drugs like favipiravir and molnupiravir.

Main Methods:

  • Investigating the effects of promutagenic nucleosides (e.g., 5-hydroxydeoxycytidine) on viral infectivity.
  • Analyzing the mutagenic potential of approved nucleoside analogs like ribavirin, favipiravir, and molnupiravir.
  • Examining the incorporation and impact of molnupiravir on viral RNA and replication fidelity.

Main Results:

  • Loss of HIV infectivity observed with specific nucleoside analogs, correlating with increased mutation rates.
  • Favipiravir and molnupiravir demonstrated broad-spectrum antiviral activity via lethal mutagenesis.
  • Molnupiravir increases G→A and C→U transition frequencies in SARS-CoV-2 RNA through incorporation and polymerase extension errors.

Conclusions:

  • Lethal mutagenesis is a viable strategy for combating RNA viruses, including HIV and SARS-CoV-2.
  • Nucleoside analogs like favipiravir and molnupiravir are effective broad-spectrum antiviral agents.
  • Carcinogenic risks and genotoxicity necessitate caution for widespread use of these mutagenic antiviral therapies.
Keywords:
HIVRNA polymeraseSARS-CoV-2error catastrophefavipiravirlethal mutagenesismolnupiravirnucleoside analogsribavirin

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