Extensive <i>In-silico</i> Target-Ligand Conformational Space Sampling of Garlic-Derived Sulfur Compounds Targeting COVID-19 Infection

The still ongoing search for effective antiviral agents against SARS-CoV-2 has led researchers to explore natural products for potential therapeutic candidates. In this work, we conducted a comprehensive high-throughput virtual screening and molecular docking analysis of twenty-six garlic-derived sulfur-containing compounds against several key viral and host targets selected because of their relevance in the SARS-CoV-2 infection cycle. We studied the binding interactions of these compounds with targets including the viral Spike complex, Mpro and PLpro and cell’s ACE2, TMPRSS2 and Cathepsin B. Our analysis revealed that compounds [Formula: see text]-glutamyl-S-t-1-propenylcysteine, [Formula: see text]-glutamyl-S-allylcysteine, cycloalliin and carvone, exhibited the most promising binding affinities, hence act as potential inhibitors by interfering the viral entry and replication processes. Notably, they also demonstrated strong binding at the RBD-ACE2 interface, suggesting their capacity to block the initial viral attachment and entry. These findings highlight the potential of garlic-derived compounds as multi-target antiviral agents, warranting further experimental validation to confirm their efficacy and explore their therapeutic potential against COVID-19.