Table3_Indian Ethnomedicinal Phytochemicals as Promising Inhibitors of RNA-Binding Domain of SARS-CoV-2 Nucleocapsid Phosphoprotein: An In Silico Study.DOCX

SARS-CoV-2, an etiological agent of COVID-19, has been the reason for the unexpected global pandemic, causing severe mortality and imposing devastative effects on public health. Despite extensive research work put forward by scientist around globe, so far, no suitable drug or vaccine (safe, affordable, and efficacious) has been identified to treat SARS-CoV-2. As an alternative way of improvising the COVID-19 treatment strategy, that is, strengthening of host immune system, a great deal of attention has been given to phytocompounds from medicinal herbs worldwide. In a similar fashion, the present study deliberately focuses on the phytochemicals of three Indian herbal medicinal plants viz., Mentha arvensis, Coriandrum sativum, and Ocimum sanctum for their efficacy to target well-recognized viral receptor protein through molecular docking and dynamic analyses. Nucleocapsid phosphoprotein (N) of SARS-CoV-2, being a pivotal player in replication, transcription, and viral genome assembly, has been recognized as one of the most attractive viral receptor protein targets for controlling the viral multiplication in the host. Out of 127 phytochemicals screened, nine (linarin, eudesmol, cadinene, geranyl acetate, alpha-thujene, germacrene A, kaempferol-3-O-glucuronide, kaempferide, and baicalin) were found to be phenomenal in terms of exhibiting high binding affinity toward the catalytic pocket of target N-protein. Further, the ADMET prediction analysis unveiled the non-tumorigenic, noncarcinogenic, nontoxic, non-mutagenic, and nonreproductive nature of the identified bioactive molecules. Furthermore, the data of molecular dynamic simulation validated the conformational and dynamic stability of the docked complexes. Concomitantly, the data of the present study validated the anti-COVID efficacy of the bioactives from selected medicinal plants of Indian origin.

SARS-CoV-2，COVID-19的病原体，成为了一场突发全球大流行的导火索，造成了极高的死亡率，并对公共卫生造成了毁灭性的影响。尽管全球科学家进行了广泛的研究工作，迄今为止，尚未发现一种安全、经济且有效的药物或疫苗来治疗SARS-CoV-2。作为一种改善COVID-19治疗策略的替代方法，即增强宿主免疫系统，全球范围内药用植物的植物化合物受到了极大的关注。本研究特此聚焦于三种印度药用植物中的植物化学成分，即薄荷（Mentha arvensis）、香菜（Coriandrum sativum）和圣罗勒（Ocimum sanctum），研究其通过分子对接和动态分析靶向已知病毒受体蛋白的效力。SARS-CoV-2的核衣壳磷酸蛋白（N蛋白）在复制、转录和病毒基因组组装中发挥着关键作用，已被认定为控制宿主体内病毒增殖的最具吸引力的病毒受体蛋白靶点之一。在筛选的127种植物化学成分中，有九种（香芹酚、愈创木酚、杜松烯、香叶基乙酸酯、α-松油烯、愈创木烯A、槲皮素-3-O-葡萄糖苷、橙皮苷和黄芩苷）在表现出对目标N蛋白催化口袋的高结合亲和力方面表现出卓越性能。此外，ADMET预测分析揭示了所识别的生物活性分子的非致癌性、非致突变性、非毒性、非诱变性及非生殖性。进一步地，分子动力学模拟的数据验证了对接复合物的构象和动态稳定性。同时，本研究的数据验证了源自所选印度药用植物的生物活性成分的抗COVID-19功效。