Antiviral Therapy for Flavivirus Infections

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Introduction: Infections with viruses in the genus Flavivirus, including West Nile, Japanese encephalitis, yellow fever, tick-borne encephalitis, Zika, and dengue virus, cause a range of conditions in humans and result in serious public health problems. These viruses may cause flu-like symptoms, encephalitis, meningitis, or paralysis. Flaviviruses have the potential to emerge more broadly in human populations. However, there are currently no specific drugs or antiviral therapies approved for the treatment of flavivirus infections in humans. Recent trials with a quadrivalent dengue virus vaccine indicated that vaccination could induce an increased risk of severe hemorrhagic disease after a subsequent natural infection. Therefore, a successful and potent therapy for flavivirus infections is needed and could have critical implications in the event of further emergence or a pandemic. Technology: Georgia State University researchers have invented a stabilized Oas1b messenger RNA (mRNA) construct and treatment method as a potentially-efficacious pan-flavivirus antiviral therapy in humans. The 2�-5� oligoadenylate synthetase (OAS) pathway functions as an innate host defense response against viral infections. Delivery of full-length Oas1b from a stabilized mRNA in a variety of human cell lines efficiently suppresses flavivirus genome RNA synthesis. The use of mRNA leads to transient expression of Oas1b to avoid long-term expression seen with DNA construct or virus vector delivery. In addition, the pre-clinical studies indicated that delivery of full-length OasIb protein in already-established flavivirus infections also results in inhibition of viral RNA amplification and clearance of the infections from the brains.