Abstract

SARS-CoV-2 is the etiological agent of COVID-19 and responsible for more than 6 million cases globally, for which no vaccine or antiviral is available. Therefore, this study was planned to investigate the antiviral role of the active constituents against spike glycoprotein of SARS-CoV-2 as well as its host ACE2 receptor. Structure-based drug design approach has been used to elucidate the antiviral activity of active constituents present in traditional medicinal plants from Ayurveda. Further, parameters like drug-likeness, pharmacokinetics, and toxicity were determined to ensure the safety and efficacy of active constituents. Gene network analysis was performed to investigate the pathways altered during COVID-19. The prediction of drug–target interactions was performed to discover novel targets for active constituents. The results suggested that amarogentin, eufoliatorin, α-amyrin, caesalpinins, kutkin, β-sitosterol, and belladonnine are the top-ranked molecules have the highest affinity towards both the spike glycoprotein and ACE2. Most active constituents have passed the criteria of drug-likeness and demonstrated good pharmacokinetic profile with minimum predicted toxicity level. Gene network analysis confirmed that G-protein coupled receptor, protein kinase B signaling, protein secretion, peptidyl-serine phosphorylation, nuclear transport, apoptotic pathway, tumor necrosis factor, regulation of angiotensin level, positive regulation of ion transport, and membrane protein proteolysis were altered during COVID-19. The target prediction analysis revealed that most active constituents target the same pathways which are found to be altered during COVID-19. Collectively, our data encourages the use of active constituents as a potential therapy for COVID-19. However, further studies are ongoing to confirm its efficacy against disease.

Communicated by Ramaswamy H. Sarma

摘要

SARS-CoV-2 是 COVID-19 的病原体，导致全球超过 600 万例病例，没有可用的疫苗或抗病毒药物。因此，本研究计划研究活性成分对 SARS-CoV-2 的刺突糖蛋白及其宿主 ACE2 受体的抗病毒作用。基于结构的药物设计方法已被用于阐明阿育吠陀传统药用植物中存在的活性成分的抗病毒活性。此外，还确定了药物相似性、药代动力学和毒性等参数，以确保活性成分的安全性和有效性。进行基因网络分析以研究 COVID-19 期间改变的途径。进行药物-靶标相互作用的预测以发现活性成分的新靶标。结果表明，amarogentin、eufoliatorin、α-amyrin、caesalpinins、kutkin、β-谷甾醇和颠茄碱是对尖峰糖蛋白和 ACE2 的亲和力最高的分子。大多数活性成分已通过药物相似性标准，并表现出良好的药代动力学特征和最低的预计毒性水平。基因网络分析证实，G蛋白偶联受体、蛋白激酶B信号通路、蛋白分泌、肽丝氨酸磷酸化、核转运、凋亡通路、肿瘤坏死因子、血管紧张素水平调节、离子转运正调节、膜蛋白水解在 COVID-19 期间发生了改变。目标预测分析显示，大多数活性成分靶向相同的途径，这些途径被发现在 COVID-19 期间发生了改变。总的来说，我们的数据鼓励使用活性成分作为 COVID-19 的潜在疗法。然而，正在进行进一步的研究以证实其对疾病的功效。

由 Ramaswamy H. Sarma 传达