Trends in Antiviral Strategies

Domingo, Esteban

Viral populations are true moving targets regarding the genomic sequences to be targeted in antiviral designs. Experts from different fields have expressed the need of new paradigms for antiviral interventions and viral disease control. This chapter reviews several strategies that aim at counteracting the adaptive capacity of viral quasispecies. The proposed designs are based on combinations of different antiviral drugs and immune modulators, or in the administration of virus-specific mutagenic agents, in an approach termed lethal mutagenesis of viruses. It consists of decreasing viral fitness by an excess of mutations that render viral proteins sub-optimal or non-functional. Viral extinction by lethal mutagenesis involves several sequential, overlapping steps that recapitulate the major concepts of intra-population interactions and genetic information stability discussed in preceding chapters. Despite the magnitude of the challenge, the chapter closes with some optimistic prospects for an effective control of viruses displaying error-prone replication, based on the combined targeting of replication fidelity and the induction of the innate immune response.