Hybrid Heterocyclic Boronic Acids
Desmond Murray (Chemistry) and Kanya Long (Biology)
Hybrid Heterocyclic Boronic Acids as Potential Inhibitors against Alphaviruses
Alphaviruses carried by mosquitoes cause diseases resulting in severe, debilitating effects in people. Recently, one alphavirus, chikungunya virus (CHIKV) has shown a shift in geographic distribution and vector affinity that has increased the public health threat of this virus. Despite this concern, there is currently no approved treatment or effective preventative methods for alphaviruses and
development of novel agents is needed.
We seek to use an interdisciplinary approach to develop and investigate hybrid heterocyclic boronic acids as potential inhibitors against alphaviruses. The literature indicates several classes of heterocycles that show antiviral activity. The novelty of our approach is to covalently attach boronic acids to heterocycles to determine whether or not increased therapeutic potency is obtained. Part of our working hypothesis is that the boronic acid group would improve attachment of the antiviral agent to the virus surface via interactions with specific glycoproteins. Boronic acid-carbohydrate interactions is a well-established and documented phenomena but has not been applied as described in our proposal. As a consequence, our proposed antiviral agents could block the virus from entering host cells and/or can initiate other inhibitory mechanisms of action.
We will use established methods from previous work in our laboratories to develop these novel compounds, and adopt methods from recent studies to assess the replication, cytopathic effect, and cell viability in mammalian cells treated with these compounds and infected with MAYV and SINV, two alphaviruses closely related to CHIKV. Success here has the potential to provide agents that can be applied to other viruses.