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宫颈癌(Cervical cancer,CC)是妇科最常见的恶性肿瘤之一,而高危型人乳头瘤病毒(Human papillomavirus,HPV)的持续感染是诱导宫颈癌发生的重要危险因素。目前全球抗HPV药物极为匮乏,寻找新的高效、低毒、价廉的广谱抗病毒药物对HPV感染的防治至关重要。本文研究发现,咖啡酸(Caffeic acid,CA)能有效抑制三株不同亚型的HPV感染(HPV-6、HPV-16及HPV-18),其半数抑制浓度在12.1~16.5μg/mL之间。Time-of-addition结果证实,咖啡酸对病毒进入靶细胞的早期阶段具有一定抑制作用。Temperature shift实验发现,咖啡酸能一定程度抑制HPV病毒颗粒黏附于靶细胞表面。表面等离子共振分析表明,咖啡酸与HPV-16型病毒的主要衣壳蛋白L1具有极强的结合力。综上,咖啡酸具有较高的抗HPV活性,其作用机制可能是与病毒衣壳蛋白L1结合,从而阻止病毒黏附并进入靶细胞。咖啡酸具有安全、价廉、易得等优势,有望被开发成新型的抗HPV病毒感染的抑制剂,因其尚能同时抵抗多种性传播性病毒的感染,对HPV并发的多种性传播性疾病具有较好的预防作用,应用前景广泛。
Abstract：Cervical cancer is a common malignant gynecologic tumor.Infection by the human papillomavirus(HPV)is the most important and dangerous factor for the development of cervical cancer.Currently,antiHPV drugs are extremely scarce.Development of highly efficacious,low-toxicity,and inexpensive broadspectrum drugs for the prevention of HPV infection is extremely important.Here,we found that caffeic acid(CA)exhibited highly potent antiviral activities against infection by three HPV subtypes(6,16 and18),with half-maximal inhibitory concentration(IC50)values of 12.1~16.5μg/mL.A time-of-addition assay suggested that CA interacted with the early stages of HPV entry into target cells.A temperatureshift assay confirmed that CA significantly inhibited the attachment of the HPV to the surface receptors of target cells.The interaction between CA and major capsid protein L1 of HPV-16 was shown by surface plasmon resonance.In summary,CA has high activity against the HPV.The interaction between CA and viral capsid L1 protein can prevent HPV attachment and entry into target cells.CA is inexpensive,safe,obtained readily with broad antiviral activities.CA could be developed as an effective and affordable antiHPV agent for prevention of sexually transmitted diseases.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.003353
中图分类号:R737.33
引用信息:
[1]丁永桢,温嘉泳,赖宝龙,等.咖啡酸抗人乳头瘤病毒感染的研究[J].病毒学报,2018,34(03):287-295.DOI:10.13242/j.cnki.bingduxuebao.003353.
基金信息:
国家自然科学基金面上项目(项目号:81673481),题目:抗CD45RO抗体-JQ1偶联物激活HIV潜伏库的作用及机制研究; 广州市白云区科技计划项目(项目号:2016-KJ-002):Apabetalone激活HIV潜伏感染的研究; 南方医科大学2017年度大学生创新创业训练计划国家级项目,题目:杨梅素对精源性病毒感染增强因子的作用及机制研究~~
2018-04-08
2018-04-08
2018-04-08