Biosketch
I am deeply honored and proud to have been part of SASTRA University, an institution that has served as both my academic home and a constant source of inspiration. Under the guidance of dedicated faculty members who not only imparted strong foundational knowledge but also nurtured my research skills, my journey has been truly transformative. Their mentorship, encouragement, and unwavering support have shaped me not only as a researcher but also as an individual with a deeper sense of curiosity, discipline, and perseverance.
Reflecting on my Ph.D. journey, I see it as a true masterclass in patience and resilience. It taught me to approach research with optimism, even when faced with limited resources. I learned to plan my work meticulously, develop a clear blueprint, and translate that vision into tangible outcomes such as research publications. Beyond academic achievements, this experience has helped me understand and navigate diverse perspectives, strengthening my empathy, adaptability, and professionalism, qualities that extend far beyond the laboratory.
Date of Award
17-8-2025
Document Type
Thesis
School
School of Chemical & Biotechnology
Programme
Ph.D.-Doctoral of Philosophy
First Advisor
Saraboji Kadhirvel
Second Advisor
Venkatasubramanian Ulaganathan
Keywords
Lymphatic Filariasis, Wuchereria Bancrofti, Subtractive Genomics, Antioxidant Enzymes, Structure-Based Drug Design
Abstract
Lymphatic filariasis (LF), or elephantiasis, is a mosquito-borne parasitic disease affecting the lymphatic system, primarily in tropical and subtropical regions. It is the second leading cause of long-term disability and a neglected tropical disease. According to WHO, LF threatens 882 million people in 44 countries, with over 9 billion treatments administered. The disease is caused by three nematodes: Wuchereria bancrofti (90% of cases worldwide, including India), Brugia malayi (10% in Southeast and Eastern Asia), and Brugia timori (found in Timor and nearby islands). Lymphatic filariasis (LF) is an ancient disease that continues to challenge scientists and physicians. Current treatments include diethylcarbamazine (DEC), albendazole (ALB), and ivermectin (IVM), but drug resistance is rising due to SNP mutations and lack of specificity with the filarial targets from repeated use. These drugs are ineffective at all stages of the parasite’s complex life cycle. There is an urgent need to identify new druggable targets and candidate molecules to combat LF effectively.
IDENTIFICATION OF PUTATIVE DRUG TARGETS OF W. BANCROFTI:
In this direction, we identified potential drug targets for W. bancrofti by analyzing its complete proteome, retrieved from NCBI and UniProt. After removing redundant sequences, BLASTp screening against the human proteome identified 8,350 non-homologous proteins, with 125 classified as essential through DEG analysis. Metabolic pathway screening revealed 12 key enzymes, including five major antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPx), peroxiredoxin 6 (Prx6), thioredoxin peroxidase 1 (Tpx1), and glutathione S-transferase (GST), critical for neutralizing reactive oxygen species (ROS) and maintaining cellular homeostasis. As these enzymes are vital for parasite survival, making them promising therapeutic targets for the development of antifilarial drugs.
MODELLING AND STRUCTURE-BASED DRUG DESIGN OF FILARIAL ANTIOXIDANT ENZYMES:
The three-dimensional structure of SOD1, GPx, Prx6 and Tpx1 was modelled and the dynamic stability from MD simulation showed that the antioxidant enzymes were found to be stable based on the trajectory profiles and the resultant structures were used for further studies. Structure-based drug design targeted filarial antioxidant enzymes using the ChemBridge database. To minimize failures, ADMET screening identified the top five non-toxic leads per enzyme with the highest docking scores. Comparative-docking against human antioxidant enzymes confirmed higher specificity for filarial targets due to differences in surface charge, cavity volume, and hydrogen bonding. The complex MD simulations confirmed the stable and intact binding of these leads in the enzyme pockets. Finally, the top three non-toxic leads per filarial antioxidant enzyme were procured for in vitro studies.
IN VITRO VALIDATION OF THE LEADS:
Antifilarial activity was tested using Setaria digitata, a homolog of W. bancrofti, authenticated at the Veterinary College, Orathanadu. The MTT-formazan assay evaluated the top three leads per target at concentrations ranging from 0.625 to 20.000 μM in triplicate, comparing their inhibition rates to ivermectin. We observed ten leads exhibit a lesser IC50 value, while the remaining five exhibit a higher IC50 value than the control drug ivermectin. The leads with lower IC50 than the control exhibited AAHR and AARR pharmacophore features, while the other leads had ADHR and AHRR, differing due to geometric variations.
CONCLUSION
Our computational results and in vitro studies identified potential leads for the five antioxidant enzymes that play a vital role in the first-line defence against free radicals and reactive oxygen species, in vitro assay revealed ten leads exhibit better antifilarial activity. Inhibiting these major antioxidant enzymes will likely reduce the pathogenicity and survival of W. bancrofti. The implication of the findings offers valuable insight. It opens up new avenues for developing novel inhibitors for further drug development and clinical trials to effectively combat lymphatic filariasis caused by W. bancrofti in India and globally. In addition, this study serves as a model pipeline for other Neglected Tropical Diseases (NTDs), to identify potential drug targets and candidate drug molecules.
Recommended Citation
M, Sureshan Mr, "Computational Studies On The Major Antioxidant Enzymes Of Wuchereria Bancrofti Towards The Development Of Anti Filarial Leads" (2025). Theses and Dissertations. 140.
https://knowledgeconnect.sastra.edu/theses/140