Computer-Assisted Drug Discovery of Potential African Anti-SARS-CoV-2 Natural Products Targeting the Helicase Protein

Abstract

Objectives: In our continuous efforts to combat COVID-19, our objective was to conduct a comprehensive computer-aided drug design study utilizing 4924 African natural metabolites sourced from diverse databases across various African regions from 1962 to 2019. The primary goal was to target the SARS-CoV-2 helicase, a crucial enzyme in viral replication. Methods: We employed structural fingerprint and molecular similarity studies with VXG, the co-crystallized ligand, as a reference. Subsequently, docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were conducted. Results: The structural fingerprint analysis identified 200 structurally similar compounds, then the molecular similarity studies selected 40 compounds. Among them, 15 metabolites with low free energies, favorable binding modes, and promising ADMET properties were identified. Four compounds were excluded according to the toxicity studies. Compound 1552, 1-(( S)-2,3-dihydro-2-(( R)-1-hydroxypropan-2-yl)benzofuran-5-yl)ethenone, exhibited the most favorable docking results. Molecular dynamics simulations conclusively demonstrated its stable binding to the SARS-CoV-2 helicase, characterized by low energy and optimal dynamics. Conclusion: The findings suggest promising avenues for potential COVID-19 cures, encouraging further exploration through in vitro and in vivo studies of the identified compounds, particularly compound 1552.