Chemical reactivity of alliin and its molecular interactions with the protease Mpro of SARS-CoV-2 Scientific paper

Abstract

In the present work, a computational study of the chemical reactivity of alliin at the X/DGDZVP level of theory (where X is B3LYP, M06, M06L or wB97XD) was performed. The distribution of active sites on alliin was deter­mined by evaluating the Fukui function. For electrophilic attacks, the more reactive sites are on the carbon atoms of the prop-2-ene moiety. The more active sites for nucleophilic attacks are located on the thioether group. In the case of free radical attacks, the more reactive sites are on the carbonyl, thio­ether and prop-2-ene moieties. Additionally, the molecular docking study rev­ealed that, alliin is able to dock to the protease M^pro of SARS-CoV-2 through interactions with the catalytic CYS145-HSD164 dyad via van der Waals inter­actions, with MET49 with interactions alkyl-type ions and with PHE140 by hydrogen bonds. Also, the molecular dynamic study indicates that alliin rem­ains in the pocket site. Last result suggests that this molecule is a potential can­didate for further in vitro evaluation as a drug for the treatment of the major protease-based SARS-CoV-2 virus.