Virtual screening of sulfur compounds of Allium against coronavirus proteases: E-Ajoene is a potential dual protease targeting covalent inhibitor

IF 2.1 3区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
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.

葱属植物硫化合物抗冠状病毒蛋白酶的虚拟筛选:E-Ajoene是一种潜在的双蛋白酶靶向共价抑制剂
减缓SARS-CoV-2的主要蛋白酶(Mpro)和木瓜蛋白酶样蛋白酶(PLpro)的活性对抗击持续致命的新冠肺炎大流行具有直接影响。这些蛋白酶的活性位点含有半胱氨酸硫醇,半胱氨酸硫醇被硫药物如依硒仑和二硫仑共价修饰。葱的天然产物含有几种活性硫化合物,这些化合物可能共价修饰冠状病毒蛋白酶的活性位点半胱氨酸硫醇。该报告通过常规对接方法评估了葱的52种不同硫化合物对冠状病毒Mpro和PLpro的结合亲和力。前六种化合物中有三种对这两种蛋白酶都表现出高亲和力,即E-阿焦烯(S3)、S-(3-戊基)-L-半胱氨酸-硫酰化物(S49)和1-丙烯基烯丙基硫代亚硫酸酯(S14)。对反应性含硫化合物E-ajoene和1-丙烯基烯丙基硫代亚磺酸盐进行了假定反应的能量学计算和共价对接研究。结果表明,它们通过S-硫烯丙基化、S-硫烯丙酯亚磺酰基丙烯基化和S-硫丙烯基化共价修饰蛋白酶的活性位点半胱氨酸硫醇。共价修饰的多样性、对蛋白酶的高亲和力和活性位点硫介导的氢键表明,E-阿霍烯是一种潜在的双蛋白酶靶向SARS-CoV-2共价抑制剂。图形摘要
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来源期刊
Journal of Sulfur Chemistry
Journal of Sulfur Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
4.10
自引率
9.10%
发文量
38
审稿时长
6-12 weeks
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.
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