Antiviral Therapy Against Mosquito-Borne Rift Valley Fever Virus

Researchers have developed a potential antiviral therapy against Rift Valley Fever Virus (RVFV) infection using sequence-selective siRNA inhibition. RVFV causes mosquito-borne illness and is recognized as a “Category A” Priority Pathogen, which affects human and animal populations in Africa and the Middle East. Although not endemic in North America and Europe, it has the potential to expand its range to these regions and is also a potential tool for bioterrorism. Currently, no effective therapy exists against RVFV. Existing antiviral drugs have been used to treat human infections, albeit with serious side effects.

DESCRIPTION:
Researchers have developed therapeutic siRNA duplexes as a potential therapy against RVFV. This siRNA-mediated therapy is expected to cause minimal or no side effects, by working to directly silence the nucleoprotein gene of the RVFV and suppress its replication. The nucleoprotein gene was specifically targeted as it is a highly conserved viral gene and less prone to mutations. Additionally, if any mutations were to occur in the viral genome, then a simple change in the nucleotide sequence of the siRNA would address the problem and provide an effective cure. Alternatively, the therapy can involve the simultaneous use of several siRNA duplexes that target different areas of the viral nucleoprotein, to further overcome any possible resistance due to mutations.

ADVANTAGES:

• Significantly inhibits viral protein expression and viral replication
• Expected to cause minimal to no side effects
• Development of resistance due to viral mutations can be easily addressed by redesigning the siRNA construct
• siRNAs specifically target the viral nucleoprotein gene, which is a highly conserved gene and less prone to mutations
• Possible mutations at the specific nucleoprotein gene locus can be overcome by the use of several siRNA duplexes that target different areas of the nucleoprotein gene

APPLICATIONS:
The RVFV-specific siRNA duplexes may be used to treat humans and animals infected with Rift Valley Fever Virus.