Abstract

The recent outbreak of SARS CoV-2 has changed the global scenario of human lives/economy. A significant number of the non-survivors showed cardiac renal vasculature dysfunction. A ‘cytokine storm’ namely, interleukin IL6–IL1 receptors, i.e. IL6R–IL1R over-functioning was reported. Here, nigellidine, an indazole alkaloid and key component of Nigella sativa L. (NS) commonly known as black cumin seed was analysed for COVID-19 protein targeting and IL1R–IL6R inhibition through molecular docking study and biochemical study in experimental rat to evaluate antioxidative capacity. The NMR/X-ray crystallographic/electron microscopic structures of COVID-19 main protease (6LU7)/spike glycoprotein (6vsb)/NSP2 (QHD43415_2)/nucleocapsid (QHD43423), human IL1R (1itb)-IL6R (1pm9) from PDB were retrieved analysed for receptor–ligand interaction. Then, those structures were docked with nigellidine using AutoDock and PatchDock server. A brief comparison was made with nigellicine thymoquinone from N. sativa. Where nigellidine showed highest binding energy of −6.6 kcal/mol, ligand efficiency of −0.3 with COVID19 Nsp2 forming bonds with amino acid CYS240 present in binding pocket. Nigellidine showed strong interaction with main protease (BE: –6.38/LE: –0.29). Nigellidine showed affinity to IL1R (–6.23). The NS treated rat showed marked decline in ALP-SGPT-SGOT-malondialdehyde (MDA) than the basal levels. From the Western blot and activity analysis, it was observed that Nigellidine (sulphuryl group drug) showed no impact on phenol-catalysing ASTIV and steroid-catalysing oestrogen-sulphotransferase expressions and activities in liver tissue and thus has no influence in sulphation-mediated adverse metabolic processes. Conclusively, nigellidine has hepato-reno-protective/antioxidant-immunomodulatory/anti-inflammatory activities with inhibit potentials of COVID-19 proteins. Further validation is necessary.

摘要

最近爆​​发的 SARS CoV-2 改变了人类生活/经济的全球格局。相当数量的非幸存者表现出心脏肾血管系统功能障碍。据报道，“细胞因子风暴”即白细胞介素 IL6-IL1 受体，即 IL6R-IL1R 功能过度。在这里，nigelidine，一种吲唑生物碱和Nigella sativa L的关键成分. (NS) 俗称黑孜然种子，通过对实验大鼠的分子对接研究和生化研究，分析 COVID-19 蛋白靶向和 IL1R-IL6R 抑制作用，以评估抗氧化能力。来自 PDB 的 COVID-19 主要蛋白酶 (6LU7)/刺突糖蛋白 (6vsb)/NSP2 (QHD43415_2)/核衣壳 (QHD43423)、人 IL1R (1itb)-IL6R (1pm9) 的 NMR/X 射线晶体学/电子显微镜结构为检索分析受体 - 配体相互作用。然后，这些结构使用 AutoDock 和 PatchDock 服务器与 Nigelidine 对接。与来自N. sativa的 nigellicine thymoquinone 进行了简要比较。其中尼格列啶显示最高结合能为 -6.6 kcal/mol，配体效率为 -0.3，COVID19 Nsp2 与结合袋中存在的氨基酸 CYS240 形成键。Nigelidine 显示出与主要蛋白酶的强相互作用 (BE: –6.38/LE: –0.29)。Nigelidine 显示出对 IL1R 的亲和力 (–6.23)。NS 处理的大鼠的 ALP-SGPT-SGOT-丙二醛 (MDA) 比基础水平显着下降。从蛋白质印迹和活性分析中观察到，Nigellidine（磺基类药物）对苯酚催化的 ASTIV 和类固醇催化的雌激素-磺基转移酶在肝组织中的表达和活性没有影响，因此对硫酸盐介导的不良代谢没有影响过程。最终，nigellidine 具有肝肾保护/抗氧化免疫调节/抗炎活性，具有抑制 COVID-19 蛋白的潜力。需要进一步验证。