title: Antiviral Strategies Based on Lethal Mutagenesis and Error Threshold.
abstract: The concept of error threshold derived from quasispecies theory is at the basis of lethal mutagenesis, a new antiviral strategy based on the increase of virus mutation rate above an extinction threshold. Research on this strategy is justified by several inhibitor-escape routes that viruses utilize to ensure their survival. Successive steps in the transition from an organized viral quasispecies into loss of biologically meaningful genomic sequences are dissected. The possible connections between theoretical models and experimental observations on lethal mutagenesis are reviewed. The possibility of using combination of virus-specific mutagenic nucleotide analogues and broad-spectrum, non-mutagenic inhibitors is evaluated. We emphasize the power that quasispecies theory has had to stimulate exploration of new means to combat pathogenic viruses.
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.|Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.|Liver Unit, Internal Medicine, Laboratori of Malalties Hepàtiques, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, 08035, Barcelona, Spain.
authors: Celia
authors: C
authors: Perales
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain. edomingo@cbm.csic.es.|Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. edomingo@cbm.csic.es.
authors: Esteban
authors: E
authors: Domingo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D006801:Humans; D016296:Mutagenesis / Q000187:drug effects*; D014777:Virus Diseases / Q000188:drug therapy / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects; D014780:Viruses / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000998:Antiviral Agents