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粉防己碱通过破坏病毒内化作用来抑制寨卡病毒。

Fangchinoline Inhibits Zika Virus by Disrupting Virus Internalization.

作者信息

Yang Shaokang, Yang Xiaotong, Wang Zhuang, Li Wei, Cao Ruiyuan, Zhong Wu

机构信息

National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.

出版信息

ACS Infect Dis. 2024 Dec 13;10(12):4066-4072. doi: 10.1021/acsinfecdis.4c00600. Epub 2024 Nov 13.

Abstract

The Zika virus (ZIKV) has garnered significant public attention, particularly following the outbreak in Brazil, due to its potential to cause severe damage to the central nervous system and its ability to cross the placental barrier, resulting in microcephaly in infants. Despite the urgency, there remains a lack of targeted therapies or vaccines for the prevention or treatment of ZIKV infection and its related diseases. Fangchinoline (FAN), an alkaloid derived from traditional Chinese medicinal herbs, has a range of biological activities. In this study, we employed both and infection models to demonstrate the efficacy of FAN in inhibiting ZIKV. Our findings indicate that FAN effectively suppresses the replication of ZIKV viral RNA and protein, thereby validating its anti-ZIKV capabilities in living organisms. Further analysis through dosing time assays and infectious inhibition assays revealed that FAN exerts its antiviral effects by impeding the early stages of infection, specifically by inhibiting the internalization of ZIKV. These results underscore the potential of FAN as a candidate for anti-ZIKV drug development and offer novel insights into drug design strategies that target the virus's internalization process.

摘要

寨卡病毒(ZIKV)已引起公众的高度关注,尤其是在巴西爆发疫情之后,因为它有可能对中枢神经系统造成严重损害,并且能够穿过胎盘屏障,导致婴儿患小头畸形。尽管情况紧急,但目前仍缺乏针对寨卡病毒感染及其相关疾病的预防或治疗的靶向疗法或疫苗。粉防己碱(FAN)是一种源自传统中草药的生物碱,具有一系列生物活性。在本研究中,我们使用了[具体模型1]和[具体模型2]感染模型来证明粉防己碱在抑制寨卡病毒方面的功效。我们的研究结果表明,粉防己碱有效地抑制了寨卡病毒的病毒RNA和蛋白质的复制,从而证实了其在活生物体中的抗寨卡病毒能力。通过给药时间试验和感染抑制试验的进一步分析表明,粉防己碱通过阻碍感染的早期阶段发挥其抗病毒作用,特别是通过抑制寨卡病毒的内化。这些结果强调了粉防己碱作为抗寨卡病毒药物开发候选药物的潜力,并为针对病毒内化过程的药物设计策略提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb27/11650651/b5ea0a8aa65f/id4c00600_0001.jpg

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