Targeting with Allicin via Dual S-Thioallylation as a Potential Therapeutic Approach for COVID-19

Abstract

According to the World Health Organization (WHO), coronavirus disease 2019 (COVID-19) is an ongoing epidemic caused by new coronavirus infections that has resulted in 3716075 deaths worldwide.The SARS-CoV-2 major protease (Mpro) is an important component of coronavirus replication and is hence a prime candidate for inhibitor discovery in COVID-19 treatment. The SARS-CoV-2 Mpro is effectively inhibited by the preclinical medicines ebselen and PX-12, which covalently modify the Mpro active site Cys-145 residue by selenosul-fide/disulfide. The reactive sulfur species allicin is subjected to covalent docking at the active site of SARS-CoV-2 M in the current work using PX-12 as a reference molecule and virtual screening methods. According to the findings, allicin causes the SARS-CoV-2 Mpro's Cys-145 and Cys-85/Cys-156 residues to undergo dual S-thioallylation. The hypothesized reactions between N-acetylcysteine amide thiol and allicin/allyl sulfenic acid are computed using density functional theory (DFT) to determine the Gibbs free energychange (DG). Overall, the reaction is exergonic, and the Mpro's Cys-145 residue's allyl disulfide is implicated in a hydrogen bond that is mediated by sulfur. According to the findings, allicin induces dual S-thioallylation of SARS-CoV-2 Mpro, which may be useful for treating and reducing persistent coronavirus infection.