Exploring Phytochemicals as Promising Lead Drug Candidates for Zika Virus: An Integrated Computational Investigation
Click the Poster to View Full Screen, Right click to save image
Siyun Yang
College:
The Dorothy and George Hennings College of Science, Mathematics, and Technology
Major:
Biology
Faculty Research Advisor(s):
Supratik Kar
Abstract:
The Zika virus (ZIKV) poses a global health threat, belonging to the Flaviviridae family and the Flavivirus genus, primarily transmitted by mosquitoes. A Zika infection can result in severe neurological disorders such as Guillain-Barré Syndrome, as well as birth defects including microcephaly, brain and eye defects, miscarriage, stillbirth, and preterm birth. It is a single-stranded positive-sense ribonucleic acid (RNA) virus with a genome of around 10.8 kilobases encoding 3419 amino acids. With no US FDA-approved drugs or vaccines available, urgent attention is needed for drug discovery to protect against the potential upcoming pandemic. The ZIKV NS2B/NS3 protein plays a critical role in the virus's replication, making it a key target for intervention. Initially, the insecticidal activity of a series of 62 plant-derived molecules against the Aedes aegypti mosquito, the vector for chikungunya, dengue, and Zika viruses, was assessed through docking studies and QSAR modeling. This was followed by a similarity search of the top 5 molecules in the Supernatural III database and the Coconut database. Identified ligands underwent XP docking using Schrödinger software. Subsequently, the top ten molecules were selected based on their docking scores for absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Four phytochemicals with the least toxicity were chosen for further investigation, subjected to a 500 ns molecular dynamics (MD) simulation study using the Desmond module, followed by an MM-GBSA study with the Prime module of Schrödinger. The phytochemicals identified, exhibiting minimal toxicity and promising ADMET profiles, present as potential lead drug candidates for Zika virus intervention.