Developing effective antivirals for the treatment of West Nile neuroinvasive disease

Arthropod-borne viruses (arboviruses) are transmitted by mosquitoes and other arthropod vectors, categorized into four virus families (Flaviviridae, Bunyaviridae, Togaviridae, and Reoviridae), causing a significant global public health burden. Yearly, arboviruses cause an estimated 700,000 deaths in humans worldwide. West Nile virus (WNV) is an arbovirus and is transmitted to humans by mosquito bites. It is a single-stranded positive-sense enveloped RNA virus, belonging to the genus Orthoflavivirus, of the Flaviviridae family, resulting in the largest epidemics of neuroinvasive WNV ever known. Most infected people are asymptomatic. In around 1% patients, virus can invade the CNS, causing a severe neurological disease, which called West Nile neuroinvasive disease (WNND). However, till now, no specific antiviral drugs are commercially available for the treatment of the West Nile neuroinvasive disease. Hence developing effective treatments as well as preventive measurements to combat life-threatening WNV infection in humans is urgent. In this project, we aim to determine whether broad-spectrum antiviral compounds, such as RDV and RBV as well as newly identified compounds, can be used to prevent the development of WNND. We will investigate the efficacy of these compounds, both single compound treatments and combinations of the compounds, in preventing/inhibiting WNV infection, both in vitro and in vivo.