Identification of neprilysin as a potential target of arteannuin using computational drug repositioning

ABSTRACT The discovery of arteannuin (qinghaosu) in the 20th Century was a major advance for medicine. Besides functioning as a malaria therapy, arteannuin is a pharmacological agent in a range of other diseases, but its mechanism of action remains obscure. In this study, the reverse docking server PharmMapper was used to identify potential targets of arteannuin. The results were checked using the chemical-protein interactome servers DRAR-CPI and DDI-CPI, and verified by AutoDock Vina. The results showed that neprilysin (also known as CD10), a common acute lymphoblastic leukaemia antigen, was the top disease-related target of arteannuin. The chemical-protein interactome and docking results agreed with those of PharmMapper, further implicating neprilysin as a potential target. Although experimental verification is required, this study provides guidance for future pharmacological investigations into novel clinical applications for arteannuin.

摘要：20世纪青蒿素（arteannuin，qinghaosu）的发现是医学领域的重大进展。除用作疟疾治疗药物外，青蒿素还可作为治疗多种其他疾病的药理活性物质，但其具体作用机制仍不明晰。本研究借助反向对接服务器PharmMapper鉴定青蒿素的潜在作用靶点，随后通过化学-蛋白质相互作用组服务器DRAR-CPI与DDI-CPI对所得结果进行校验，并利用AutoDock Vina完成验证。结果显示，脑啡肽酶（neprilysin，亦称CD10）——一种常见的急性淋巴细胞白血病抗原——是与疾病相关的青蒿素排名首位的作用靶点。化学-蛋白质相互作用组分析结果与分子对接结果均与PharmMapper的分析结果一致，进一步佐证脑啡肽酶为青蒿素的潜在作用靶点。尽管仍需开展实验验证以确认该结论，但本研究为未来探索青蒿素新型临床应用的药理学研究提供了重要指导。