title: My Cousin, My Enemy: quasispecies suppression of drug resistance.
abstract: If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections, newly synthesized viral genomes occupy the same cells as parent and other progeny genomes. If the antiviral target is chosen so that the drug-resistant progeny's growth is dominantly inhibited by the drug-susceptible members of its intracellular family, its outgrowth can be suppressed. Precedent for 'dominant drug targeting' as a deliberate approach to suppress the outgrowth of inhibitor-resistant viruses has been established for envelope variants of vesicular stomatitis virus and for capsid variants of poliovirus and dengue virus. Small molecules that stabilize oligomeric assemblages are a promising means to an unfit family to destroy the effectiveness of a newborn drug-resistant relative due to the co-assembly of drug-susceptible and drug-resistant monomers.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: karlak@stanford.edu.
authors.forename: Karla
authors.initials: K
authors.lastname: Kirkegaard
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: van Buuren
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mateo
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D003716:Dengue Virus / Q000187:drug effects / Q000502:physiology*; D024882:Drug Resistance, Viral; D005828:Genetics, Population; D006801:Humans; D017955:Poliovirus / Q000187:drug effects / Q000502:physiology*; D012641:Selection, Genetic; D018116:Vesiculovirus / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents