Table4_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，作为COVID-19的致病因子，引发了全球突发性大流行，造成了极高的死亡率，并对公共卫生造成了毁灭性的影响。尽管全球科学家们进行了广泛的研究工作，但截至目前，尚未发现能够有效治疗SARS-CoV-2的药物或疫苗（既安全、经济又有效）。作为改进COVID-19治疗策略的替代途径，即增强宿主免疫系统，全球范围内对药用植物中的植物化学成分的关注度显著提升。本研究特意聚焦于三种印度药用植物的植物化学成分，即薄荷（Mentha arvensis）、香菜（Coriandrum sativum）和圣罗勒（Ocimum sanctum），以探究其通过分子对接和动态分析针对已知的病毒受体蛋白的疗效。SARS-CoV-2的核壳磷蛋白（N）作为复制、转录和病毒基因组组装的关键参与者，已被认定为控制病毒在宿主体内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（即薄荷脑、莰烯、香茅醇乙酸酯、α- thuene、 germacrene A、槲皮素-3-O-葡萄糖苷、异槲皮素、黄芩苷）表现出对目标N蛋白催化口袋的高结合亲和力。此外，ADMET预测分析揭示了所识别的生物活性分子的非致瘤性、非致癌性、非毒性、非致突变性和非生殖性。进一步地，分子动力学模拟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来自所选印度药用植物的生物活性成分的COVID-19抗病毒疗效。