Administration of E2 and NS1 siRNAs Inhibit Chikungunya Virus Replication In Vitro and Protects Mice Infected with the Virus

<div><p>Background</p><p>Chikungunya virus (CHIKV) has reemerged as a life threatening pathogen and caused large epidemics in several countries. So far, no licensed vaccine or effective antivirals are available and the treatment remains symptomatic. In this context, development of effective and safe prophylactics and therapeutics assumes priority.</p><p>Methods</p><p>We evaluated the efficacy of the siRNAs against ns1 and E2 genes of CHIKV both <i>in vitro</i> and <i>in vivo</i>. Four siRNAs each, targeting the E2 (Chik-1 to Chik-4) and ns1 (Chik-5 to Chik-8) genes were designed and evaluated for efficiency in inhibiting CHIKV growth <i>in vitro</i> and <i>in vivo</i>. Chik-1 and Chik-5 siRNAs were effective in controlling CHIKV replication <i>in vitro</i> as assessed by real time PCR, IFA and plaque assay.</p><p>Conclusions</p><p>CHIKV replication was completely inhibited in the virus-infected mice when administered 72 hours post infection. The combination of Chik-1 and Chik-5 siRNAs exhibited additive effect leading to early and complete inhibition of virus replication. These findings suggest that RNAi capable of inhibiting CHIKV growth might constitute a new therapeutic strategy for controlling CHIKV infection and transmission.</p>