COVID-19 pandemic causative SARS-CoV-2 coronavirus is still rapid in progression and transmission even after a year. Understanding the viral transmission and impeding the replication process within human cells are considered as the vital point to control and overcome COVID-19 infection. Non-structural Protein 1, one among the proteins initially produced upon viral entry into human cells, instantly binds with the human ribosome and inhibit the host translation process by preventing the mRNA attachment. However, the formation of NSP1 bound Ribosome complex does not affect the viral replication process. NSP1 plays an indispensable role in modulating the host gene expression and completely steals the host cellular machinery. The full-length structure of NSP1 is essential for the activity in the host cell and importantly the loop connecting N and C-terminal domains are reported to play a role in ribosome binding. Due to the unavailability of the experimentally determined full-length structure of NSP1, we have modelled the complete structure using comparative modelling and the stability and conformational behaviour of the modelled structure was evaluated through molecular dynamics simulation. Interestingly, the present study reveals the significance of the inter motif loop to serves as a potential binding site for drug discovery experiments. Further, we have screened the phytochemicals from medicinal plant sources since they were used for several hundred years that minimizes the traditional drug development time. Among the 5638 phytochemicals screened against the functionally associated binding site of NSP1, the best five phytochemicals shown high docking score of −9.63 to −8.75 kcal/mol were further evaluated through molecular dynamics simulations to understand the binding affinity and stability of the complex. Prime MM-GBSA analysis gave the relative binding free energies for the top five compounds (dihydromyricetin, 10-demethylcephaeline, dihydroquercetin, pseudolycorine and tricetin) in the range of −45.17 kcal/mol to −37.23 kcal/mol, indicating its binding efficacy in the predicted binding site of NSP1. The density functional theory calculations were performed for the selected five phytochemicals to determine the complex stability and chemical reactivity. Thus, the identified phytochemicals could further be used as effective anti-viral agents to overcome COVID-19 and as well as several other viral infections.

COVID-19 大流行病原性 SARS-CoV-2 冠状病毒即使在一年后仍在快速发展和传播。了解病毒传播并阻止人体细胞内的复制过程被认为是控制和克服 COVID-19 感染的关键。非结构蛋白 1 是病毒进入人体细胞后最初产生的一种蛋白质，它会立即与人体核糖体结合，并通过阻止 mRNA 附着来抑制宿主翻译过程。然而，NSP1 结合核糖体复合物的形成并不影响病毒复制过程。NSP1 在调节宿主基因表达中起着不可或缺的作用，并完全窃取了宿主细胞机制。NSP1 的全长结构对于宿主细胞中的活性至关重要，重要的是连接 N 和 C 末端结构域的环据报道在核糖体结合中发挥作用。由于实验确定的 NSP1 全长结构不可用，我们使用比较建模对完整结构进行建模，并通过分子动力学模拟评估建模结构的稳定性和构象行为。有趣的是，本研究揭示了基序间环作为药物发现实验的潜在结合位点的重要性。此外，我们已经从药用植物来源中筛选了植物化学物质，因为它们已经使用了数百年，从而最大限度地缩短了传统药物的开发时间。在针对 NSP1 的功能相关结合位点筛选的 5638 种植物化学物质中，最好的五种植物化学物质显示出 -9.63 至 -8.75 kcal/mol 的高对接分数，通过分子动力学模拟进一步评估，以了解复合物的结合亲和力和稳定性。Prime MM-GBSA 分析给出了前五种化合物（二氢杨梅素、10-去甲基头孢碱、二氢槲皮素、假石榴碱和三醋酮）的相对结合自由能在-45.17 kcal/mol 到-37.23 kcal/mol 的范围内，表明其结合功效NSP1 的预测结合位点。对选定的五种植物化学物质进行密度泛函理论计算，以确定复杂的稳定性和化学反应性。因此，