Lethal mutagens: broad-spectrum antivirals with limited potential for development of resistance?
RNA virus populations display extreme sequence variation. It is thought that this heterogeneity is advantageous to the population, permitting adaptation to rapidly changing environments that present varying types and degrees of selective pressure. A consequence of this efficient evolution of RNA viruses is the susceptibility of these viruses to compounds that further increase sequence variation as these agents force the virus into error catastrophe. Therefore, lethal mutagenesis, induction of error catastrophe, represents an important, untapped strategy for development of antiviral agents. This article briefly describes the theoretical and experimental data supporting lethal mutagenesis as an antiviral strategy and discusses host and viral mechanisms for development of resistance to ribavirin, a representative of this class of antiviral agents.
Freistadt
Marion S
MS
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA.
Meades
Glen D
GD
Cameron
Craig E
CE
D000998:Antiviral Agents / Q000009:adverse effects*; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016254:Mutagenesis, Insertional / Q000187:drug effects*; D012367:RNA, Viral / Q000187:drug effects*; D012254:Ribavirin / Q000009:adverse effects
D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin