TY - JOUR
T1 - The increasing impact of lethal mutagenesis of viruses
AU - Perales, Celia
AU - Gallego, Isabel
AU - De Ávila, Ana Isabel
AU - Soria, María Eugenia
AU - Gregori, Josep
AU - Quer, Josep
AU - Domingo, Esteban
PY - 2019/7
Y1 - 2019/7
N2 - © 2019 Newlands Press. Selection of viral mutants resistant to compounds used in therapy is a major determinant of treatment failure, a problem akin to antibiotic resistance in bacteria. In this scenario, mutagenic base and nucleoside analogs have entered the picture because they increase the mutation rate of viral populations to levels incompatible with their survival. This antiviral strategy is termed lethal mutagenesis. It has found a major impulse with the observation that some antiviral agents, which initially were considered only inhibitors of virus multiplication, may in effect exert part of their antiviral activity through mutagenesis. Here, we review the conceptual basis of lethal mutagenesis, the evidence of virus extinction through mutagenic nucleotide analogs and prospects for application in antiviral designs.
AB - © 2019 Newlands Press. Selection of viral mutants resistant to compounds used in therapy is a major determinant of treatment failure, a problem akin to antibiotic resistance in bacteria. In this scenario, mutagenic base and nucleoside analogs have entered the picture because they increase the mutation rate of viral populations to levels incompatible with their survival. This antiviral strategy is termed lethal mutagenesis. It has found a major impulse with the observation that some antiviral agents, which initially were considered only inhibitors of virus multiplication, may in effect exert part of their antiviral activity through mutagenesis. Here, we review the conceptual basis of lethal mutagenesis, the evidence of virus extinction through mutagenic nucleotide analogs and prospects for application in antiviral designs.
KW - antiviral drugs
KW - error catastrophe
KW - viral quasispecies
UR - http://www.mendeley.com/research/increasing-impact-lethal-mutagenesis-viruses
U2 - 10.4155/fmc-2018-0457
DO - 10.4155/fmc-2018-0457
M3 - Article
C2 - 31469331
SN - 1756-8919
VL - 11
SP - 1645
EP - 1657
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 13
ER -