Research Projects

The dengue virus (DENV) poses a major public health challenge, causing millions of infections annually and emphasizing the need for alternative therapeutic strategies. Recent studies on host-virus interactions have underscored the critical role of host ion channels (HICs) in modifying ion flow to support viral needs, a mechanism also exploited by viruses like SARS-CoV-2 and Influenza A. These viruses utilize HICs for essential functions, including ion exchange, which supports viral replication by disrupting cellular homeostasis. For instance, recent studies have identified TRPV4 ion channel as a regulator of DDX3X-dependent RNA metabolism and viral infectivity. In the case of DENV, prior studies have identified voltage-gated calcium channels and two-pore domain potassium channels as important factors for viral replication. However, comprehensive studies exploring interactions that correlate with infection severity are lacking. Additionally, anti-viral activity of ion channel-blockers was reported, illustrating the potential of drug repurposing. For instance, a recent study reported that the pharmacological inhibition of TRPV4 with HC067047 reduces the infectivity of hepatitis C, dengue and Zika viruses. Given the above knowledge gap, the present proposal aims to develop a detailed interaction map of DENV-host ion channel (DENV-HIC) protein-protein interactions using machine learning (ML) approaches. Through this approach, the study will identify specific ion channels exploited by DENV proteins, providing insights into potential ion channel blockers capable of disrupting critical DENV-HIC interactions. The study will further evaluate the action of ion channel blockers in controlling dengue infection at the acute phase using in vitro models. Thus, this study will be a pioneering scientific effort to systematically explore DENV proteins-ion channel interactions, paving the way for alternative treatment strategies for dengue infection.