分子对接和动力学研究表明:木瓜叶提取物中的植物化学物质可作为SARS-CoV-2蛋白靶点和tnf - α和凝血酶人类靶点的潜在抑制剂,用于对抗COVID-19

IF 0.7 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY AIMS Molecular Science Pub Date : 2023-01-01 DOI:10.3934/molsci.2023015
Mohd Shukri Abd Shukor, Mohd Yunus Abd Shukor
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引用次数: 1

摘要

& lt; abstract>应对COVID-19需要遏制病毒增殖并减少病毒在人类中的并发症。木瓜叶提取物(PLE)以其在体外抑制大量病毒复制的能力而闻名。和<italic>in vivov </italic>减少人类的病毒并发症,如血小板减少症和细胞因子风暴。本研究的目的是通过100 ns分子动力学模拟(MDS)方法进行硅对接,评估木瓜叶提取物作为COVID-19多方面抗病毒和潜在治疗的可能用途。目标蛋白是SARS-CoV-2的蛋白,如核衣壳、主蛋白酶(MPro)、RNA依赖性RNA聚合酶(RdRP)、刺突蛋白(武汉、德尔塔和欧米克隆变体)和人类tnf - α和凝血酶α靶点。从PLE中提取的一些化合物,如原薯蓣皂苷、阴蒂素、甘草酸、山楂林、山奈酚- 3 - (2g -葡萄糖-芦丁苷)、芦丁、异槲皮素和猕猴桃酸,与这些靶标具有很强的结合性。与核衣壳、主要蛋白酶(MPro)、RdRP和刺状蛋白的最佳PLE化合物原硅酸苷(Autodock)结合自由能分别为-13.83、-13.19、-11.62和-10.77 kcal/mol (Omicron),而与tnf - α和凝血酶的结合自由能分别为-13.64和-13.50 kcal/mol。计算得到的原山药苷的抑制常数分别为216.34、27.07、73.28和99.93 nM,在纳摩尔范围内,RdRp和spike protein (Omicron)分别为3.02和12.84 nM。原薯蓣皂苷与所有蛋白靶点的关键残基相互作用。通过分子动力学模拟验证了其结合亲和姿态。利用分子力学-泊松-玻尔兹曼表面积(MM-PBSA)计算的结合亲和力分析表明,原硅酸钠与所有靶标之间具有良好的相互作用,基于总无结合能证实了Autodock的对接结果。综上所述,从PLE中提取的化合物,特别是原薯蓣皂苷具有良好的抗COVID-19潜力。</p>& lt; / abstract>
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Molecular docking and dynamics studies show: Phytochemicals from Papaya leaves extracts as potential inhibitors of SARS–CoV–2 proteins targets and TNF–alpha and alpha thrombin human targets for combating COVID-19

Tackling COVID-19 requires halting virus proliferation and reducing viral complications in humans. Papaya leaf extract (PLE) is well known for its ability to inhibit numerous viral replications in vitro and in vivo and reduce viral complications in humans such as thrombocytopenia and cytokine storm. The goal of this research is to evaluate the possible use of papaya leaf extract as a multifaceted antiviral and potential therapy for COVID-19 using an in-silico docking followed by a 100 ns molecular dynamics simulation (MDS) approach. The targeted proteins are the SARS-CoV-2's proteins such as the nucleocapsid, main protease (MPro), RNA-dependent RNA polymerase (RdRP), spike protein (Wuhan, Delta, and Omicron variants) and human TNF-alpha and alpha-thrombin protein targets. Several compounds from PLE such as protodioscin, clitorin, glycyrrhizic acid, manghaslin, kaempferol–3–(2g–glucosylrutinoside), rutin, isoquercetrin and acacic acid were found to exhibit strong binding to these targets. The free energies of binding (Autodock) with protodioscin, the best PLE compound for nucleocapsid, main protease (MPro), RdRP and spike protein were –13.83, –13.19, –11.62 and –10.77 (Omicron), kcal/mol, respectively, while the TNF-alpha and alpha-thrombin binding free energies were –13.64 and –13.50 kcal/mol, respectively. The calculated inhibition constants for protodioscin were in the nanomolar and picomolar range at 216.34, 27.07, 73.28, and 99.93 pM, respectively, whilst RdRp and spike protein (Omicron) were in the nanomolar range at 3.02 and 12.84 nM, respectively. Protodioscin interacted with key residues of all protein targets. The binding affinity poses were confirmed by molecular dynamics simulation. Analysis of the binding affinities calculated employing the molecular mechanics-Poisson–Boltzmann surface area (MM-PBSA) shows favorable interaction between protodioscin, and all targets based on total binding-free energies corroborating the Autodock's docking results. In conclusion, compounds from PLE, especially protodioscin have good potentials in combating COVID-19.

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AIMS Molecular Science
AIMS Molecular Science BIOCHEMISTRY & MOLECULAR BIOLOGY-
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