Abstract：
Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.
摘要：
基孔肯雅热是由基孔肯雅病毒（CHIKV）引起的急性传染病，由伊蚊传播。它的特点是发烧，皮疹和关节痛没有有效的药物。洛美利嗪(Lomerizine,Lom)是新一代钙拮抗剂,主要用于治疗偏头痛。一些研究显示了Lom的某些抗病毒功能。在我们的研究中,设计并合成了Lom的一系列新衍生物，并对其体外抗CHIKV活性进行了测试。结果表明，Lom及其衍生物具有较强的抗CHIKV活性和较低的细胞毒性。其中,化合物B1和B7显示出最有效的抗病毒活性。此外,结构-活动关系，还分析了硅胶ADMET的性能。进行分子对接研究以合理化SAR并分析B1和nsP3蛋白活性位点中氨基酸残基之间的可能结合模式，以增强对其作为抗病毒剂的作用的理解。这些发现为设计和合成以Lom为先导化合物的有效抗CHIKV药物提供了研究依据。
