To accelerate the Zika beat: Candidate design for RNA interference-based therapy

Zika virus infection is associated with the development of severe neurological disorders in adults and newborns. Although at the moment Zika virus outbreak is not threatening to become again an emergency, infection cases are still being sporadically reported and there is still no effective therapy available. A possible treatment to suppress Zika replication is represented by short interfering RNAs (siRNAs), since they have been successfully used even against Ebola, H5N1 and SARS viruses and clinical trials of siRNA-based drugs are ongoing. In order to speed up the time consuming experimental validation of effective siRNAs, we have performed a comprehensive bioinformatic analysis to design only a few promising siRNAs against Zika virus. Besides siRNA efficacy, we paid attention to broad-spectrum antiviral activity, obtained by analysing all known Zika genomes, and siRNA safety, by excluding siRNAs that could potentially provoke an immune response or interfere with host mRNAs, lncRNAs, circRNAs and RNA binding proteins. In Zika genome we identified several highly conserved regions targetable by only 20 siRNAs. In particular, only a few siRNAs survived highly stringent criteria for siRNA safety. Notably, two of our candidate siRNAs have been successfully used against other flaviviruses like Zika, both in in vitro and in vivo models. Since they were effective against two different flaviviruses, by targeting a highly conserved region, it is reasonable to hypothesize that they could be active also against Zika. Therefore, we encourage researchers to experimentally validate these promising siRNAs.