Shamasoddin Shekh , Smriti Moi , Konkallu Hanumae Gowd
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引用次数: 1
Abstract
Mitigation of the activity of the main protease (Mpro) and papain-like protease (PLpro) of SARS CoV-2 has direct implications in combating the ongoing deadly COVID-19 pandemic. The active site of these proteases contains cysteine thiols which are covalently modified by the sulfur drugs such as ebselen and disulfiram. The natural product of Allium contains several reactive sulfur compounds that may covalently modify the active site cysteine thiols of coronavirus proteases. The report has assessed the binding affinity of the 52 different sulfur compounds of Allium against both Mpro and PLpro of coronavirus by conventional docking methods. Three of the top six compounds have demonstrated high affinity for both the proteases, namely, E-ajoene (S3), S-(3-pentanyl)-L-cysteine-sulfoxide (S49), and 1-propenyl allyl thiosulfinate (S14). The reactive sulfur compounds E-ajoene and 1-propenyl allyl thiosulfinate were subjected to the calculation of energetics of the putative reactions and covalent docking studies. The results indicate they covalently modify the active site cysteine thiols of the proteases through S-thioallylation, S-thioallyl sulfinyl propenylation, and S-thiopropenylation. The diversity of covalent modifications, high affinity for both the proteases and sulfur-mediated hydrogen bonds at the active site indicate that E-ajoene is a potential dual protease targeting covalent inhibitor of SARS CoV-2.
期刊介绍:
The Journal of Sulfur Chemistry is an international journal for the dissemination of scientific results in the rapidly expanding realm of sulfur chemistry. The journal publishes high quality reviews, full papers and communications in the following areas: organic and inorganic chemistry, industrial chemistry, materials and polymer chemistry, biological chemistry and interdisciplinary studies directly related to sulfur science.
Papers outlining theoretical, physical, mechanistic or synthetic studies pertaining to sulfur chemistry are welcome. Hence the target audience is made up of academic and industrial chemists with peripheral or focused interests in sulfur chemistry. Manuscripts that truly define the aims of the journal include, but are not limited to, those that offer: a) innovative use of sulfur reagents; b) new synthetic approaches to sulfur-containing biomolecules, materials or organic and organometallic compounds; c) theoretical and physical studies that facilitate the understanding of sulfur structure, bonding or reactivity; d) catalytic, selective, synthetically useful or noteworthy transformations of sulfur containing molecules; e) industrial applications of sulfur chemistry; f) unique sulfur atom or molecule involvement in interfacial phenomena; g) descriptions of solid phase or combinatorial methods involving sulfur containing substrates. Submissions pertaining to related atoms such as selenium and tellurium are also welcome. Articles offering routine heterocycle formation through established reactions of sulfur containing substrates are outside the scope of the journal.