Postdoctoral Research Projects
PhD Research Projects
The BBB membrane permeability of some of the natural compounds was studied at the atomic level to understand the passage mechanism. Neurotherapeutic drugs frequently fail in clinical trials due to low permeability and bioavailability. Therefore in this study, a computational model of the blood-brain barrier (BBB) was used to investigate how different lipid components affect the ability of natural compounds - Withaferin-A (Wi-A), Withanone (Wi-N), Caffeic Acid Phenethyl Ester (CAPE), and Artepillin-C (ARC) - to passively penetrate the BBB. These compounds are known for their therapeutic properties in brain-related disorders, but their ability to cross the BBB has not been experimentally demonstrated. Therefore, steered molecular dynamics simulations and umbrella sampling was used to calculate the energy profile, diffusion coefficient, and permeability coefficient of these compounds as they are passed through the BBB bilayer membrane.
The antiviral potential of natural compounds was studied. Specifically, the natural compounds which may be beneficial against SARS-CoV-2. Overall, structure-based computational analyses were performed to predict the effect of honeybee propolis-derived compounds (CAPE: Caffeic Acid Phenethyl Ester and ARC: Artepillin C) and Ashwagandha-derived Withanolides on virus-host cell surface receptors. Cell-based assays were employed to investigate the effect of these compounds on the expression level of the target proteins and virus replication. Nine Ashwagandha-derived Withanolides were tested in silico for their potential to target and inhibit TMPRSS2 receptor and viral main protease Mpro. It was found that most Withanolides possess the capacity to bind to TMPRSS2 and Mpro. On the other hand, CAPE and ARC showed stable interactions at the active site of Mpro. ARC, but not CAPE, showed stable interaction with TMPRSS2. Human cells treated with Withanolides, CAPE and ARC showed downregulation of the receptor. Furthermore, cell- and PCR-based SARS-CoV-2 replication assays endorsed the antiviral activity of the compounds.
It explores the anti-cancer potential of the ashwagandha and honey bee propolis-derived compounds. The first part of the study was to investigate the effect of Withaferin-A, Withanone and Caffeic Acid Phenethyl Ester on DNA methyltransferases (DNMTs). DNMTs have been identified as promising targets for drug development in various cancers. However, a significant obstacle in developing effective inhibitors of DNMTs is the limited understanding of the various forms of DNMTs and their specific roles in promoting hypermethylation in cancer cells. Lack of information on specificity, stability and the higher toxicity of previously reported DNMT inhibitors are the reasons for inadequate epigenetic cancer therapy. DNMT1 and DNMT3A are the two majorly overexpressed DNMTs in cancers. Therefore, computational and experimental analyses are carried out to assess the potential of natural compounds - Withaferin A (Wi-A), Withanone (Wi-N) and Caffeic Acid Phenethyl Ester (CAPE) as inhibitors of DNMT in comparison to Sinefungin (SFG) (a known dual inhibitor of DNMT1 and DNMT3A).
The second part of this project focuses on identifying the top protein targets of bioactive molecules in Ashwagandha and studying their molecular mechanism of action. The typical drug discovery method involves screening a compound library against a single therapeutic target, disregarding potential off-target effects. However, to reduce off-target effects, a new approach was taken. By using inverse screening and structure-based molecular dynamics, this study aimed to find the best protein target for Withanolides and understand their interactions. Withanolides were screened against multiple targets using ligand shape-based inverse screening and network analysis. The PDE4D was found to be the best target for Withanolides due to its binding interactions, energy, and dynamics.
B.Tech Final Year Project
For this project, Tulsi (Ocimum sanctum) and Neem (Azadirachta indica) were chosen to compare their antimicrobial activity towards gram-positive (S.aureus) and gram-negative bacteria (E.coli) as nowadays microbial resistance is increasing against various antibiotics and synthetic drugs, so antimicrobial metabolites can be used to overcome this resistance and can prevent and cure various infective diseases. Methanolic leaf extract of both neem and tulsi has shown significant antimicrobial activity towards both gram-positive and gram-negative bacteria, from statistical analysis it has been seen that tulsi was more effective towards S.aureus while neem was more effective towards E.coli. The Minimum Inhibitory Concentration (MIC) of tulsi and neem extract for both E.coli and S.aureus was 0.4gm/ml and 0.2 gm/ml respectively. When both extracts were mixed with each other they have shown a linear or better effect towards both bacteria and MIC also got reduced to 0.2 gm/ml. This antimicrobial activity is definitely because of secondary metabolites present in them, so we have tested for six biochemicals namely flavonoids, tannins, saponins, sterols, glycosides, and anthraquinones by taking the references from previous literature, but more study is needed in the area of the mechanism of action of each metabolite towards microbial activity.
Students co-mentored
Pallavi Rao (Amity University, Noida): Evaluating the potential of natural compounds to inhibit the activity Of wild type and the mutant form of EGFR.
Aditya Rathi (IIT Delhi): Identification of withanolides with potential as phosphodiesterase-4 (PDE4D) inhibitor. (Received Bose Research Award)
Himanshu (IIT Delhi): Inhibitory potential of natural molecules against Spike-hACE2 interactions of SARS-CoV-2 mutants.
Harit Kohli (IIT Delhi): Structural Analysis of the Human ZP2 Protein and its Mutants: Insights into Dynamics and Stability.
Teaching Assistant during PhD
As a TA I conducted the basic bioinformatics laboratory for the undergraduate students at IIT Delhi. During the classes, I taught the practical implementation of bioinformatics tools and databases such as NCBI, BLAST, CLUSTALW, Genome browser, PDB, Uniprot etc.
As a TA I conducted the basic Genomics laboratory for the undergraduate students at IIT Delhi. I taught the basics of Linux commands and Galaxy tools for the next generation sequencing data analysis.