Exploring Phytocompounds’ Interaction with Multi-Serotype Dengue Virus NS5-MTase: Insights into Binding Affinity and Activity
Indian Journal of Pharmaceutical Education and Research
Abstract
Background: Dengue Virus (DENV) infection poses a formidable global health threat, spanning from mild breakbone fever to severe conditions such as dengue hemorrhagic fever and dengue shock syndrome. The NS5-MTase enzyme assumes a pivotal role in DENV replication by catalyzing methylation at guanine N7 and ribose 2'-OH during viral cap structure formation. Materials and Methods: Targeting the MTase presents a promising strategy for combating flavivirus infections. In recent years, plant-derived metabolites have garnered attention for their antiviral properties, particularly flavones and flavonoids, which have shown efficacy against the DENV MTase protein. Results: This study seeks to identify phytocompound capable of interacting with multiple DENV serotypes. Employing a combination of docking, molecular dynamics, and QSAR techniques, we identified potent inhibitors of the NS5-MTase protein. Our investigation identified a flavonoid exhibiting high binding affinity towards the MTase protein across major DENV serotypes. Conclusion: Furthermore, molecular dynamics simulations and QSAR analysis were employed to assess the stability of molecular interactions and predicted activity, respectively; shedding light on the potential of the identified phytocompound with calculated IC50 of 76.009 nM as a therapeutic agent against MTase of DENV infection
Keywords
- Baicalin
- Dengue
- Methyltransferase
- Molecular Dynamics simulations
- QSAR
- Virtual screening