Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening,...

Area of Science:

• Biochemistry
• Computational Biology
• Pharmacology

Background:

• Dengue fever is a significant global health issue with limited treatment options.
• Developing broad-spectrum anti-dengue agents targeting all four serotypes remains a challenge.
• Phytocompounds are explored as potential antiviral agents due to their diverse bioactivity.

Purpose of the Study:

• To investigate phytocompounds as potential dengue antivirals targeting the dengue virus non-structural 2B and non-structural 3 protease (NS2B-NS3pro).
• To identify potent phytocompounds with high binding affinity to the NS2B-NS3pro target using computational methods.

Main Methods:

• A virtual screening of over 300 antiviral phytocompounds was performed.
• Molecular docking and toxicity evaluations were conducted against the NS2B-NS3pro target.
• The top docked compounds underwent molecular dynamics simulations and binding free energy calculations.

Main Results:

• Thirty phytocompounds with anti-dengue properties were identified and virtually screened.
• Naringin, hesperidin, gossypol, maslinic acid, and rhodiolin showed significant binding affinities.
• Maslinic acid exhibited a strong binding affinity of -8.5 kcal/mol to NS2B-NS3pro.

Conclusions:

• Maslinic acid is proposed as a potent bioactive antiviral agent for developing phytocompound-based dengue therapies.
• Computational screening of phytocompounds offers a viable strategy for discovering novel dengue antivirals.
• This research highlights the potential of natural compounds in combating dengue fever.