Antiviral Drug Discovery Project
The vast area of antiviral drug discovery is a highly multi-disciplinary venture and can be broadly classified into various research sub-disciplines, such as organic synthesis, computational drug modeling, structural & biochemical analyses of enzymes (drug target), and medicinal & pharmaceutical assessments of chemicals; each one itself a stand-alone specialized area. Our research projects encompass all of these areas and offer opportunities for multi-disciplinary trainings and skill developments.
Focus Area 1: Organic Synthesis
Synthesis of pharmacophoric units such as benzisothiazoles, chromenes, coumarines, quinolines, isoquinolines, and several other N-, S- and O-containing heterocyclic compounds and their hybrid structures are currently pursued in multistep synthetic sequences of 3-5 steps. The objective is to synthesize computationally designed molecular fragments for the purpose of screening them in our antiviral and anticancer biochemical assays (as described in the relevant section). In the long run, these structures are subjected to computational or STD-NMR spectroscopy-based insights fine-tuning to enhance their medicinal properties
Learning Skills: organic synthesis; chromatographic purification; spectroscopy-based structure elucidation.
Some of the molecules that we have synthesized or under construction
Focus Area 2: Antiviral Drug Discovery by Targeting Viral Proteases
Virus encoded proteases are essential factors for the reproduction of viral particles. Our hypothesis is that the small organic molecules that can inhibit the specific proteolytic activity of viral protease have potential to be developed into antiviral therapeutics. Towards this direction, we design, synthesize, and screen small organic molecules for their potential to inhibit the viral protease. To achieve this goal, we investigate the published crystal/NMR structures of viral proteases and based on the chemical landscape of the binding cavities, we design small organic molecules that can enhance the specific chemical interactions with the side chains of the binding cavity. Due the current pandemic of COVID-19 and prevalent dengue fever, our current focus of is on the antiviral drug discovery against SARS-COV-2, Dengue virus, and related viruses.
Learning Skills: Molecular docking, organic synthesis, high throughput screening biochemical assays.
Focus Area 3: Computational Modeling and Simulation Studies
To support our experimental data, we perform computational analyses to delineate the intriguing details of atomic level molecular interactions between the targeted protein and bound molecules. Molecular docking analyses reveal the binding modes and poses of the bound molecules in the binding cavity. The docking analyses are further substantiated by MM-GBSA and MM-PBSA level protein dynamical and simulation investigations.
Learning Skills: Molecular docking, Protein dynamics and simulations, DFT-B3LYP methods for theoretical optimization of small molecules