Potential inhibitors for SARS-CoV-2 Mpro from marine compounds

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• SARS-CoV-2 main protease is a key target for antiviral therapies.
• Natural compounds offer a promising source for developing novel inhibitors.
• Marine fungi represent an underexplored reservoir of bioactive molecules.

Purpose of the Study:

• To identify natural compounds from marine fungi with inhibitory activity against SARS-CoV-2 main protease.
• To evaluate the binding affinity of these compounds using computational methods.
• To assess the potential of these compounds as antiviral agents.

Main Methods:

• In silico screening of eleven marine fungi compounds using AutoDock Vina.
• Fast Pulling of Ligand (FPL) simulations to assess binding free energy.
• Receiver Operating Characteristic-Area Under the Curve (ROC-AUC) analysis for inhibitor classification.

Main Results:

• Eleven marine fungi compounds were identified as potential inhibitors of SARS-CoV-2 main protease.
• Four compounds (M15, M8, M11, M9) showed high predicted ligand-binding free energies (-9.87 to -9.35 kcal mol⁻¹).
• AutoDock Vina demonstrated efficiency for large-scale screening, while FPL excelled in inhibitor classification.

Conclusions:

• Marine fungi compounds, particularly M15, M8, M11, and M9, are promising candidates for SARS-CoV-2 inhibition.
• Computational approaches like Vina and FPL are valuable tools for rapid drug discovery.
• Further experimental validation is warranted to confirm the antiviral efficacy of these identified compounds.