Key result
RNAi therapeutics for RNA viruses face major challenges driven by rapid evolution and resistance mutations.
While RNAi shows potential as an antiviral therapeutic, its high specificity combined with the rapid evolution of RNA virus quasispecies frequently leads to viral escape and resistance.
Advises caution against RNAi antivirals for RNA viruses; leaves open strategies to counter resistance in future designs.
Due to high mutation rates, populations of RNA viruses exist as a collection of closely related mutants known as a quasispecies. A consequence of error-prone replication is the potential for rapid adaptation of RNA viruses when a selective pressure is applied, including host immune systems and antiviral drugs. RNA interference (RNAi) acts to inhibit protein synthesis by targeting specific mRNAs for degradation and this process has been developed to target RNA viruses, exhibiting their potential as a therapeutic against infections. However, viruses containing mutations conferring resistance to RNAi were isolated in nearly all cases, underlining the problems of rapid viral evolution. Thus, while promising, the use of RNAi in treating or preventing viral diseases remains fraught with the typical complications that result from high specificity of the target, as seen in other antiviral regimens.
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Presloid et al. (2015) conducted a review in RNA virus infections. RNA interference (RNAi) was evaluated. RNA interference (RNAi) therapeutics for RNA viruses face significant challenges due to rapid viral evolution and the frequent emergence of resistance mutations.
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