Next Article in Journal
Human Norovirus Induces Aquaporin 1 Production by Activating NF-κB Signaling Pathway
Previous Article in Journal
Low-Cost and Rapid Method of DNA Extraction from Scaled Fish Blood and Skin Mucus
Previous Article in Special Issue
Specific Interaction of DARPin with HIV-1 CANTD Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane
Review

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

1
Unité de Recherche UR17ES30 “Génomique, Biotechnologie et Stratégies Antivirales”, Institut Supérieur de Biotechnologie, Université de Monastir, Monastir 5000, Tunisia
2
Centro de Biología Molecular “Severo Ochoa” (Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid), 28049 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Graciela Andrei
Viruses 2022, 14(4), 841; https://doi.org/10.3390/v14040841
Received: 22 February 2022 / Revised: 11 April 2022 / Accepted: 13 April 2022 / Published: 18 April 2022
(This article belongs to the Special Issue Antiviral Molecular Mechanisms)
In RNA viruses, a small increase in their mutation rates can be sufficient to exceed their threshold of viability. Lethal mutagenesis is a therapeutic strategy based on the use of mutagens, driving viral populations to extinction. Extinction catastrophe can be experimentally induced by promutagenic nucleosides in cell culture models. The loss of HIV infectivity has been observed after passage in 5-hydroxydeoxycytidine or 5,6-dihydro-5-aza-2′-deoxycytidine while producing a two-fold increase in the viral mutation frequency. Among approved nucleoside analogs, experiments with polioviruses and other RNA viruses suggested that ribavirin can be mutagenic, although its mechanism of action is not clear. Favipiravir and molnupiravir exert an antiviral effect through lethal mutagenesis. Both drugs are broad-spectrum antiviral agents active against RNA viruses. Favipiravir incorporates into viral RNA, affecting the G→A and C→U transition rates. Molnupiravir (a prodrug of β-d-N4-hydroxycytidine) has been recently approved for the treatment of SARS-CoV-2 infection. Its triphosphate derivative can be incorporated into viral RNA and extended by the coronavirus RNA polymerase. Incorrect base pairing and inefficient extension by the polymerase promote mutagenesis by increasing the G→A and C→U transition frequencies. Despite having remarkable antiviral action and resilience to drug resistance, carcinogenic risks and genotoxicity are important concerns limiting their extended use in antiviral therapy. View Full-Text
Keywords: lethal mutagenesis; error catastrophe; nucleoside analogs; ribavirin; favipiravir; molnupiravir; RNA polymerase; SARS-CoV-2; HIV lethal mutagenesis; error catastrophe; nucleoside analogs; ribavirin; favipiravir; molnupiravir; RNA polymerase; SARS-CoV-2; HIV
Show Figures

Figure 1

MDPI and ACS Style

Hadj Hassine, I.; Ben M’hadheb, M.; Menéndez-Arias, L. Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity. Viruses 2022, 14, 841. https://doi.org/10.3390/v14040841

AMA Style

Hadj Hassine I, Ben M’hadheb M, Menéndez-Arias L. Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity. Viruses. 2022; 14(4):841. https://doi.org/10.3390/v14040841

Chicago/Turabian Style

Hadj Hassine, Ikbel, Manel Ben M’hadheb, and Luis Menéndez-Arias. 2022. "Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity" Viruses 14, no. 4: 841. https://doi.org/10.3390/v14040841

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop