Abstract：
The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it an attractive target for antiviral drug development. In this study, the natural products from Echinacea angustifolia were retrieved for structure-based virtual screening against JEV-RdRp. The top six compounds (Echinacoside, Echinacin, Rutin, Cynaroside, Quercetagetin 7-glucoside, and Kaempferol-3-glucoside) were obtained based on the highest negative docking score, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and molecular interaction. The computational analysis of these selected compounds against the co-crystallized ligands, i.e., ATP and GTP, were performed. Further, 100 ns molecular dynamic simulation and post-free binding energy calculation of all the selected compounds complexed with JEV-RdRP were performed to check the stability of the complexes. The obtained results showed considerable stability and intermolecular interaction with native ligand-binding site residues of JEV-RdRp. Hence, selected natural compounds are admissible inhibitors of JEV-RdRp protein and can be considered for future antiviral drug development studies.
摘要：
日本脑炎病毒（JEV），一种蚊子传播的黄病毒，会导致病毒性脑炎，导致神经损伤，是大多数亚洲国家的主要威胁。病毒基因组中存在的RNA依赖性RNA聚合酶(RdRp)是基因组复制的关键成分,使其成为抗病毒药物开发的有吸引力的目标。在这项研究中,从紫锥菊中提取的天然产物用于基于结构的针对JEV-RdRp的虚拟筛选。前六种化合物（Echinacoside，Echinacin,芦丁,Cynaroside,槲皮素7-葡萄糖苷，和山奈酚-3-葡萄糖苷）是根据最高的阴性对接得分获得的，ADMET(吸收，分布，新陈代谢，排泄,和毒性)，和分子相互作用。这些选定的化合物对共结晶配体的计算分析，即，ATP和GTP，被执行了。Further,对所有与JEV-RdRP络合的所选化合物进行100ns分子动力学模拟和自由后结合能计算，以检查复合物的稳定性。获得的结果显示了相当大的稳定性和与JEV-RdRp的天然配体结合位点残基的分子间相互作用。因此，选择的天然化合物是JEV-RdRp蛋白的可接受抑制剂，可以考虑用于未来的抗病毒药物开发研究。
