Bioprospection for antiviral compounds from selected medicinal plants against RNA polymerase of rotavirus A using molecular modelling and density functional theory

IF 3.8 Q2 CHEMISTRY, PHYSICAL Chemical Physics Impact Pub Date : 2024-09-23 DOI:10.1016/j.chphi.2024.100745
Adedayo Ayodeji Lanrewaju, Abimbola Motunrayo Folami, Saheed Sabiu, Feroz Mahomed Swalaha
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Abstract

Rotavirus A (RVA) infection remains a significant global health challenge, especially in developing countries, causing severe dehydrating diarrhoea in children under five years of age. Despite the availability of four World Health Organization (WHO) pre-qualified vaccines, their availability, particularly in low-income countries, pose significant challenges. Currently, there are no specific anti-rotaviral medications hence, the urgency to develop novel therapeutics against rotavirus infection. Thus, this study explored the potential of secondary metabolites of Spondias mombin, Macaranga barteri and Dicerocaryum eriocarpum as novel inhibitors of the RNA-dependent RNA polymerase (VP1) of rotavirus A using computational techniques. Pharmacokinetics parameters were adopted to screen the top 20 metabolites with high affinity for the target, initially identified through a docking study. Furthermore, the ability of the resulting compounds to modulate the investigated target was assessed using molecular dynamics (MD) simulation, while density functional theory (DFT) calculations were conducted to predict the molecular properties of the top-ranked compounds. Except for ellagic acid hexoside (-33.14 kcal/mol), all the leads had higher binding free energy values relative to sofosbuvir (-36.58 kcal/mol) following a 120 ns MD simulation. Overall, the resulting complexes with the lead compounds demonstrated acceptable stability, reduced flexibility and compactness, with spiraeoside (-51.02 kcal/mol) displaying more favourable thermodynamics metrics, albeit with a lesser binding free energy relative to chrysoeriol 7-glucuronide (-58.36 kcal/mol). The binding free energy and thermodynamic parameters of the top-hit compounds could be attributed to their respective bond interactions and molecular orbital properties except chrysoeriol 7-glucuronide, with a need for additional structural adjustment to enhance its thermodynamic properties. Thus, these findings indicate the potential modulatory ability of the lead compounds against the VP1 protein of RVA, underscoring the importance of further in vitro and in vivo studies to validate the predicted activity, and ongoing efforts are being made to pursue this line of investigation.

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利用分子建模和密度泛函理论,从精选药用植物中寻找抗轮状病毒 A 的 RNA 聚合酶的生物抗病毒化合物
A 型轮状病毒 (RVA) 感染仍然是全球健康面临的一个重大挑战,尤其是在发展中国家,它会导致五岁以下儿童严重脱水性腹泻。尽管有四种世界卫生组织(WHO)预认证的疫苗,但它们的可用性,尤其是在低收入国家的可用性,构成了重大挑战。目前,还没有特效的抗轮状病毒药物,因此,开发新型疗法来治疗轮状病毒感染迫在眉睫。因此,本研究利用计算技术探讨了 Spondias mombin、Macaranga barteri 和 Dicerocaryum eriocarpum 的次生代谢物作为轮状病毒 A 的 RNA 依赖性 RNA 聚合酶(VP1)新型抑制剂的潜力。采用药代动力学参数筛选出与目标物亲和力较高的前 20 种代谢物,这些代谢物最初是通过对接研究确定的。此外,还利用分子动力学(MD)模拟评估了所得化合物调节研究靶标的能力,并进行了密度泛函理论(DFT)计算,以预测排名靠前的化合物的分子特性。除了鞣花酸己苷(-33.14 kcal/mol)外,所有先导化合物在 120 ns MD 模拟后的结合自由能值都高于索非布韦(-36.58 kcal/mol)。总体而言,与先导化合物形成的复合物表现出了可接受的稳定性、较低的柔韧性和紧凑性,其中螺旋苷(-51.02 kcal/mol)显示出了更有利的热力学指标,尽管其结合自由能相对于 Chrysoeriol 7-葡萄糖醛酸苷(-58.36 kcal/mol)较低。除 Chrysoeriol 7-葡萄糖醛酸外,其他热门化合物的结合自由能和热力学参数可归因于它们各自的键相互作用和分子轨道特性,需要进行额外的结构调整以提高其热力学特性。因此,这些研究结果表明先导化合物对 RVA 的 VP1 蛋白具有潜在的调节能力,强调了进一步进行体外和体内研究以验证预测活性的重要性。
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来源期刊
Chemical Physics Impact
Chemical Physics Impact Materials Science-Materials Science (miscellaneous)
CiteScore
2.60
自引率
0.00%
发文量
65
审稿时长
46 days
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