Vaccines and Antivirals
Discovery of universal vaccines and novel antivirals are the only effective countermeasures against viral pandemics. With this motivation, we are working to identify broadly cross-reactive future vaccine candidates as well as novel antiviral drugs against influenza and other RNA viruses including SARS-CoV-2, Dengue, Japanese Encephalitis Virus (JEV). Using the information obtained from our basic science research we aim to develop long standing sustainable solutions to control future RNA virus outbreaks.
1. An indigenous antibody as the potential future vaccine candidate against the yet to emerge SARS-like coronaviruses.
India has implemented the world's second largest vaccine drive and encountered a large number of breakthrough infections (infection followed by vaccination). To elucidate the humoral response triggered by these breakthroughs, we studied a cohort of 164 breakthrough infection patients in terms of the breadth and potency of their antibodies. Though longitudinal sampling of a smaller subset of volunteers, we identified sera that showed broad neutralizing efficacy against all major SARS-CoV-2 variants. Epitope mapping analysis revealed that these broadly cross reactive sera targets a novel cryptic epitope which remains conserved across all SARS-CoV-2 variants and also for different SARS-like beta coronaviruses with potential of causing future zoonotic outbreaks.
Breakthrough infection sera isolated from individuals in India during early 2022 target the conserved cryptic class 5 epitope to counteract immune escape by SARS-CoV-2 variants including the most recent emergent variant XBB1.5
Publication details:
I Das Jana, K Kanjo, S Roy, M Bhasin, S Bhattacharya, I Banerjee, S Jana, Chatterjee A, Chakraborty A, Chakraborty S, Mukherjee B, Varadarajan R, Mondal A*. Early 2022 breakthrough infection sera from India target the conserved cryptic class 5 1 epitope to counteract immune escape by SARS-CoV-2 variants. bioRxiv preprint doi:
2. Novel thiazole compounds broadly inhibiting flavivirus NS3 protease
Flaviviruses are responsible for viral hemorrhagic fevers (VHFs) throughout the world. In tropical and subtropical regions of the world, dengue (DV), Japanese encephalitis (JEV), West Nile (WNV), yellow fever (YFV), and zika viruses are among the most prevalent mosquito-borne human diseases. In our lab, we are investigating thiazole compounds for their effectiveness in broadly inhibiting flavivirus NS3 protease. Using biochemical and cell-based assays, we are extensively characterizing these compounds to assess their ability to inhibit viral protease activity and viral RNA synthesis, using dengue and Japanese encephalitis viruses as model virus systems.
Inhibitory effects of the anti-viral compounds on Flavivirus infection: Compound 3au and 3aq inhibits the action of NS3 protease thereby hampering the cleavage of long viral polyprotein hence halting the formation of individual non-structural proteins that guides the assembly of viral replication complex thereby blocking the viral replication process and prevents overall virion assembly and infection progression.