Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study

Area of Science:

• Computational chemistry
• Virology
• Drug discovery

Background:

• Dengue virus outbreaks pose a global health crisis with no specific antiviral treatments.
• Existing treatments are limited, necessitating the search for novel therapeutic agents.

Purpose of the Study:

• To identify potent inhibitors of Dengue virus infection using in silico virtual screening and molecular dynamics.
• To explore phytochemical compounds as potential antiviral agents against Dengue.

Main Methods:

• Generated a phytochemical library for virtual screening against Dengue's NS2B/NS3 protein target.
• Conducted docking studies and MM-GBSA calculations to evaluate binding affinities.
• Performed molecular dynamics simulations to analyze complex stability and interactions.

Main Results:

• Identified Phellodendroside, quercimeritrin, and quercetin-7-O-rutinoside as top-ranked inhibitors based on binding free energy.
• Observed key interactions of compounds with active site residues (Lys74, Asn152, Gln167) of NS2B/NS3.
• Molecular dynamics simulations confirmed stable docked complexes with favorable pharmacological properties and no predicted toxicity.

Conclusions:

• This computational study successfully identified promising phytochemical inhibitors for Dengue virus.
• The findings provide a foundation for developing new antiviral drugs targeting the NS2B/NS3 protein.
• In silico methods are valuable for accelerating the discovery of novel Dengue therapeutics.