In silico allicin induced S-thioallylation of SARS-CoV-2 main protease

Shekh, Shamasoddin; Reddy, K. Kasi Amarnath; Gowd, Konkallu Hanumae

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused due to new coronavirus infection with (3)716075 deaths across the world as reported by the World Health Organization (WHO). SARS-CoV-2 main protease (M(pro)) plays a vital role in the replication of coronavirus and thus an attractive target for the screening of inhibitors for the therapy of COVID-19. The preclinical drugs ebselen and PX-12 are potent inhibitors of SARS-CoV-2 M(pro) and covalently modifies the active site Cys-145 residue of M(pro) through selenosulfide/disulfide. In the current report, using virtual screening methods, reactive sulfur species allicin is subjecting for covalent docking at the active site of SARS-CoV-2 M(pro) using PX-12 as a benchmark reference compound. The results indicate that allicin induces dual S-thioallylation of Cys-145 and Cys-85/ Cys-156 residues of SARS-CoV-2 M(pro). Using density functional theory (DFT), Gibbs free energy change (DG) is calculated for the putative reactions between N-acetylcysteine amide thiol and allicin/allyl sulfenic acid. The overall reaction is exergonic and allyl disulfide of Cys-145 residue of M(pro) is involved in a sulfur mediated hydrogen bond. The results indicate that allicin causes dual S-thioallylation of SARS-CoV-2 M(pro) which may be of interest for treatment and attenuation of ongoing coronavirus infection.