title: Administration of E2 and NS1 siRNAs inhibit chikungunya virus replication in vitro and protects mice infected with the virus.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We evaluated the efficacy of the siRNAs against ns1 and E2 genes of CHIKV both in vitro and in vivo. 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 in vitro and in vivo. Chik-1 and Chik-5 siRNAs were effective in controlling CHIKV replication in vitro as assessed by real time PCR, IFA and plaque assay.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute of Virology, Microbial Containment Complex, Sus Road, Pashan, Pune, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Parashar
authors.forename: Mandar S
authors.initials: MS
authors.lastname: Paingankar
authors.forename: Satyendra
authors.initials: S
authors.lastname: Kumar
authors.forename: Mangesh D
authors.initials: MD
authors.lastname: Gokhale
authors.forename: A B
authors.initials: AB
authors.lastname: Sudeep
authors.forename: Sapana B
authors.initials: SB
authors.lastname: Shinde
authors.forename: V A
authors.initials: VA
authors.lastname: Arankalle
mesh_terms: D018354:Alphavirus Infections / Q000628:therapy* / Q000821:virology; D000818:Animals; D001688:Biological Products / Q000008:administration & dosage* / Q000378:metabolism; D001691:Biological Therapy / Q000379:methods; D002646:Chikungunya virus / Q000187:drug effects / Q000254:growth & development*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D016896:Treatment Outcome; D014709:Vero Cells; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D001688:Biological Products; D034741:RNA, Small Interfering; D014764:Viral Proteins
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