Fangchinoline Inhibits Zika Virus by Disrupting Virus Internalization.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL ACS Infectious Diseases Pub Date : 2024-11-13 DOI:10.1021/acsinfecdis.4c00600
Shaokang Yang, Xiaotong Yang, Zhuang Wang, Wei Li, Ruiyuan Cao, Wu Zhong
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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 in vitro and in vivo 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.

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方棘霉素通过干扰病毒内化抑制寨卡病毒
由于寨卡病毒(ZIKV)可能对中枢神经系统造成严重损害,并能穿过胎盘屏障,导致婴儿小头畸形,因此引起了公众的极大关注,尤其是在巴西寨卡病毒爆发之后。尽管情况紧急,但目前仍缺乏用于预防或治疗 ZIKV 感染及其相关疾病的靶向疗法或疫苗。方胆宁(FAN)是一种从传统中草药中提取的生物碱,具有一系列生物活性。在这项研究中,我们采用了体外和体内感染模型来证明 FAN 在抑制 ZIKV 方面的功效。我们的研究结果表明,FAN 能有效抑制 ZIKV 病毒 RNA 和蛋白的复制,从而验证了其在生物体内抗 ZIKV 的能力。通过剂量时间测定和感染抑制测定进行的进一步分析表明,FAN 是通过阻碍感染的早期阶段,特别是通过抑制 ZIKV 的内化来发挥其抗病毒作用的。这些结果凸显了 FAN 作为抗 ZIKV 药物开发候选物的潜力,并为针对病毒内化过程的药物设计策略提供了新的见解。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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