Research Projects

Flaviviruses are a diverse family of enveloped viruses that pose significant global health threats, particularly in tropical and subtropical regions. Dengue virus (DENV), transmitted by mosquitoes, is prevalent in India and contributes to morbidity and mortality rates. Currently, there are no approved therapeutics for DENV. Viral assembly in the host is a critical step during disease progression, presenting an opportunity for intervention. The DENV capsid protein performs multiple functions, including localizing to the endoplasmic reticulum (ER) for viral assembly, as well as lipid droplets and the nucleus. Its multifaceted role in disease propagation renders the capsid an ideal target for developing therapeutic interventions. Despite the availability of high-resolution capsid structures, fundamental questions persist regarding the capsid’s interactions with host membranes during assembly. To investigate the intricacies of capsid-membrane interactions, this study will employ advanced solution NMR spectroscopy techniques, including residual dipolar couplings and paramagnetic relaxation enhancement techniques. These methods, in conjunction with membrane mimetics, such as nanodiscs, will facilitate the acquisition of detailed structural and mechanistic insights into the engagement of the capsid with membrane bilayers. Complementary biochemical experiments, such as lipid mixing assays, will be conducted to examine the functional dynamics of lipid interactions, while site-directed mutagenesis will identify and validate key residues involved in membrane binding. This research aims to generate the first membrane-bound structural model of flavivirus capsid proteins, providing crucial insights into the early stages of viral assembly. By filling these gaps in flavivirus assembly, this research seeks to elucidate the molecular mechanisms underlying the lifecycle of these viruses. The findings from this work may potentially lead to the development of novel antiviral strategies that target the assembly process.