TY - JOUR
T1 - Lethal mutagens
T2 - Broad-spectrum antivirals with limited potential for development of resistance?
AU - Freistadt, Marion S.
AU - Meades, Glen D.
AU - Cameron, Craig E.
N1 - Funding Information:
We thank Raul Andino for comments on the manuscript. We thank Jason D. Graci for providing Fig. 2B and Christian Castro for providing Fig. 3 . C.E.C. is the recipient of an Established Investigator Award (0340028N) from the American Heart Association. Support for this work was provided, in part, by a grant (AI54776 from NIAID, NIH to C.E.C).
PY - 2004/2
Y1 - 2004/2
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=1842555264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842555264&partnerID=8YFLogxK
U2 - 10.1016/j.drup.2003.12.003
DO - 10.1016/j.drup.2003.12.003
M3 - Article
C2 - 15072768
AN - SCOPUS:1842555264
SN - 1368-7646
VL - 7
SP - 19
EP - 24
JO - Drug Resistance Updates
JF - Drug Resistance Updates
IS - 1
ER -
