Challenges for the development of ribonucleoside analogues as inducers of error catastrophe.
RNA viruses are responsible for numerous human diseases; some of these viruses are also potential agents of bioterrorism. In general, the replication of RNA viruses results in the incorporation of at least one mutation per round of replication, leading to a heterogeneous population, termed a quasispecies. The antiviral nucleoside ribavirin has been shown to cause an increase in the mutation frequency of RNA viruses. This increase in mutation frequency leads to a loss of viability due to error catastrophe. In this article, we review lethal mutagenesis as an antiviral strategy, emphasizing the challenges remaining for the development of lethal mutagenesis into a practical clinical approach.
Graci
Jason D
JD
Department of Biochemistry & Molecular Biology, Pennsylvania State University, University Park, Pa., USA.
Cameron
Craig E
CE
D000818:Animals; D015195:Drug Design; D016679:Genome, Viral; D006801:Humans; D016296:Mutagenesis / Q000187:drug effects* / Q000235:genetics; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology; D012328:RNA Viruses / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D012254:Ribavirin / Q000737:chemistry / Q000494:pharmacology; D012263:Ribonucleosides / Q000737:chemistry* / Q000494:pharmacology*
D009153:Mutagens; D012263:Ribonucleosides; D012254:Ribavirin