Abstract Summary/Description
Arenaviruses are segmented negative-strand RNA viruses listed as highly pathogenic and as potential pandemic threats by the Center for Disease Control and Prevention (CDC) and the World Health Organization (WHO). They cause severe hemorrhagic fevers, including Lassa fever (case fatality rate up to 15%) and Bolivian hemorrhagic fever ( 35% case fatality rate). Currently, no effective vaccines or specific treatments exist, except for limited efficacy of ribavirin treatment in early stages. Therefore, developing potent inhibitors against these viruses is crucial. A key mechanism employed by arenaviruses to invade host cells is "cap snatching." This process involves stealing the 5' cap structure from host mRNAs, enabling the viral RNA-dependent RNA polymerase (RdRp) to initiate viral mRNA synthesis to replicate the negative-sense genome. Our lab aims to develop effective antiviral treatments against arenaviruses by targeting their cap snatching mechanism. Through endonuclease enzyme inhibition studies, we have identified novel and promising compounds that will be further optimized through X-ray crystallography and other studies for potential drug development. We thank our collaborators in The Midwest Antiviral Drug Discovery Center (AViDD) for the partnership and support. This work is supported by an NIH grant (1U19AI171954 - 01) and a CDT/GSU fellowship to Oluwafoyinsola O. Faniyi.
