Title:Exploration and Validation of Lead Molecules against Yellow Fever
through High Throughput Virtual Screening and Molecular Dynamics
Simulation
Volume: 21
Issue: 8
Author(s): Nachammai Kathiresan, Sangavi Pandi, Thameema Parveen Sahul, Gowtham Kumar Subbaraj, Priyanka Ganapathy, Kirubhanand Chandrashekar and Langeswaran Kulanthaivel*
Affiliation:
- Department of Bioinformatics, Cancer Genetics & Molecular Biology Laboratory, Science Campus, Alagappa University,
Karaikudi, Tamil Nadu, India
Keywords:
Yellow fever, virtual screening, XP docking, molecular dynamics, HOMO-LUMO, ADME.
Abstract:
Background: Yellow fever (YF) is a mosquito-borne flaviviral hemorrhagic fever (VHF) that
causes severe hepatitis, renal failure, bleeding, and quick terminal events such as shock and multi-organ
failure. There are currently no particular anti-viral medications for the management of the YF virus
(YFV). Despite the availability of a commercial YFV vaccination, there are roughly 30,000 fatalities
globally each year, with instances rising over the previous 20 years. After being translocated into the endoplasmic
reticulum lumen, glycosylated NS1 resides as a membrane-associated dimer, where it is required
for viral genome replication. The secreted hexamer NS1 has a role in immune evasion and pathogenesis
and has been discovered as a possible diagnostic marker for the early identification of viral infections.
Objective: The main aim of this study is to analyze the small molecule as a potent drug candidate against
the target NS1 protein.
Methods: In this study, Computational approaches, including high throughput virtual screening, molecular
docking, and dynamics simulation, were carried out against the target NS1 protein using three different
chemical libraries Enamine, Asinex, and NCI. The selected lead compounds were validated through
HOMO-LUMO analysis, ADME prediction, and Toxicity parameters to analyze the biological and pharmacological
properties of the lead small molecules.
Results: From the result, it was concluded that the leads possessed the highest docking scores, interacting
with the binding residues, and were stable in the simulation period.
Conclusion: Overall findings revealed that the lead three small molecules could act as the potential drug
candidate for the target NS1 protein to inhibit the diseasing efficacy of Yellow fever.
