抗埃博拉病毒药物研究近期动态

对抗埃博拉病毒新药的近期研究成果以及业界提出或可用于治疗埃博拉出血热的已上市药物进行总结归纳,旨在为抗埃博拉病毒药物的进一步开发及埃博拉出血热治疗方案的探索提供参考。     

抗乙型肝炎病毒的天然药物研究

如何从丰富的天然生物中筛选具有抗乙型肝炎病毒活性的药物 ,并且研究它们的作用机理 ,寻找特异性强、毒副作用小的药物 ,是我国中药现代化的一个重要研究方向。本文综述了近年来中草药和一些重要的天然化合物抗乙型肝炎病毒的作用机理以及体内外研究和临床应用 ,并提出了在抗乙型肝炎病毒药物筛选中存在的一些问题     

天然药物中抗HIV活性成分研究进展

天然产物往往具有独特的化学结构,是发现新药或药物先导物的重要途径之一.目前,从天然药物中发现了多种结构类型的具有抗HIV活性的化合物,如多糖类、生物碱类、香豆素类、黄酮类、木脂素类、醌类、酚酸类、萜类等,并且其作用机制并不局限于抑制逆转录酶或蛋白酶,可在HIV复制周期的各个环节发挥作用,本文按天然产物的结构类型进行归纳,综述了近年来源自天然药物的抗HIV活性成分研究进展,总结了的151个具有抗HIV活性的天然产物结构及其活性测试数据,以期为从天然化学成分中寻找、发现并研究开发有效的抗艾滋病药物提供线索.     

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<正>2014年2月,西非埃博拉出血热疫情暴发,来势汹汹,迅速蔓延,几内亚、利比里亚、塞拉利昂、尼日利亚……人们的恐慌情绪不断加剧,全世界都在焦灼于没有有效的抗埃博拉病毒药物。在灾难面前,人类不甘束手就范,各国医药研发机构和国际药企巨头纷纷加入了抗埃博拉疫苗和治疗药物的研发大军。埃博拉离我们并不遥远,在可能出现输入性埃博拉病例国家进行的预测排名中,中国排名16位。在抗击埃博拉疫情中,我国实现了国内防控"零输入"和中国埃博拉医疗队援非抗疫的"零感染"。     

抗HIV活性天然产物

自从1981年发现获得性免疫缺陷病(AIDS)起,一直受到科学界重视.对抗人免疫缺陷病毒(HIV)药物进行了大量的研究.本文综述最近抗HIV活性天然产物的研究进展.     

埃博拉病毒侵染细胞机制的研究进展

埃博拉病毒能在人类和非人灵长类中引起严重的埃博拉出血热,病死率可高达90%,并且目前还没有针对埃博拉病毒有效的疫苗或者是治疗手段。面对埃博拉病毒带来的挑战,针对埃博拉病毒的相关研究已经成为病毒学的热点问题。其中,关于埃博拉病毒侵染细胞机制的科学研究对于开发病毒疫苗以及新型治疗药物有非常关键的作用。因此,本综述拟就埃博拉病毒侵染细胞机制方面的研究进展进行总结。     

美国抗埃博拉病毒疫苗研究获重大进展

美国国立卫生研究院的科学家于 2 0 0 0年 11月 30日宣布 ,他们在抗埃博拉病毒研究方面获重大进展 ,所开发的疫苗已成功地使猴子抵御致命的埃博拉出血热病达 6个月之久 ,这是首次对灵长类动物试验获得成功 ,这一方法将为人类最终战胜这可怕瘟疫的侵袭开辟了一条新的道路。埃博拉病毒感染性极强 ,可通过握手、咳嗽和打喷嚏等多种途径传播 ,一旦被感染 ,患者表现出高烧和体内大出血等病症 ,并在 1～ 3周内毙命。由于目前尚无任何一种抗病毒药物对它有效 ,而且它在自然界中的宿主也未查明 ,无法通过环境控制其蔓延 ,迄今为止 ,医学界认为最有效…     

Cell:研究首次发现抵抗埃博拉病毒的人广谱性抗体

正在一项新的研究中,通过分析2013~2016年埃博拉病毒爆发的一名存活者的血液,研究人员发现首个天然的人抗体能够中和所有三种主要的致病性埃博拉病毒,并且保护动物免受它们的感染。这些发现可能导致人们开发出首个广泛有效的埃博拉病毒药物和疫苗。相关研究结果发表在Cell期刊上,论文标题为"Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses"。     

抗肠道病毒71型的药物研究进展

肠道病毒71型（Enterovirus 71,EV71）是引起重症手足口病（Hand,Foot and Mouth Disease,HFMD）的主要病原体。重症HFMD进展迅速,可表现为严重的神经系统并发症,甚至危及生命。目前临床上防治EV71感染缺乏特异、高效的药物,其残疾率和死亡率很高。随着研究的深入,已经发现了大量具有抗EV71能力的化合物,人们探索的药物机制和药物靶点各不相同。因此,本文从药物靶向病毒、宿主等角度出发,针对抗EV71感染的天然药物、合成药物及常见中药中活性成分作用机制的最新进展进行综述与讨论。此外,对抗病毒药物筛选技术进行简要概述,以期为抗EV71药物的筛选与研发设计等相关研究提供参考。     

抗新冠肺炎药物研究进展

新冠病毒引发的急性呼吸道传染病造成了全球大流行的新冠肺炎,严重危害世界公共卫生安全,迫切需要研发有效治疗新冠肺炎的药物。综述了疫情暴发初期抗新冠肺炎药物研发的进展,重点介绍“老药新用”、小分子及抗体创新药物研发和中药等。通过“老药新用”研究发现多个老药具有抑制新冠病毒复制作用,其中瑞德西韦、法匹拉韦、氯喹和羟氯喹等进入临床研究,尤其是瑞德西韦成为被美国FDA批准用于新冠肺炎治疗的首个药物。针对新冠病毒识别宿主细胞受体的S蛋白开展的抗体发现和靶向3CL蛋白酶及RNA依赖的RNA聚合酶等新冠病毒复制过程中的关键蛋白质开展小分子抑制剂发现是抗新冠肺炎创新药物研究中的主要方向。此外,中药在防治新冠肺炎中发挥了重要作用,金花清感颗粒、莲花清瘟胶囊、血必净注射液、双黄连口服液、清肺排毒汤、化湿败毒方、宣肺败毒方等都进入了新冠肺炎治疗的临床研究及应用。     

Recent progress on the treatment of Ebola virus disease with Favipiravir and other related strategies

Ebola virus is one of the most threatening pathogens with the mortality rate as high as 90% in the world. There are no licensed therapeutic drugs or preventive vaccines for Ebola hemorrhagic fever up to date. Favipiravir, a novel antiviral drug which was mainly used for the treatment of influenza, now has been demonstrated to have a curative effect in treating Ebola virus infection. In this review, we present an overview of recent progress on the treatment of Ebola virus disease with Favipiravir and describe its possible mechanism. Moreover, we give a brief summary of other related treatment strategies against Ebola.     

Nucleoprotein-based indirect enzyme-linked immunosorbent assay(indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus

Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.     

Nucleoprotein-based indirect enzyme-linked immunosorbent assay (indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus

Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays (ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in anti-Ebola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G (IgG) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA’s ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.     

埃博拉病毒疫苗rVSV-ZEBOV的研究进展

埃博拉病毒被列为A类病原体,感染后可引起埃博拉出血热,具有高传染率和高致死率。研发安全有效的抗病毒疫苗迫在眉睫。目前正在研发的埃博拉病毒疫苗包括病毒载体疫苗、蛋白疫苗、DNA疫苗等,其中最有希望的是重组水疱性口炎病毒载体疫苗rVSV-ZEBOV。该疫苗在预防和治疗埃博拉出血热方面具有较高的安全性和有效性,有望在2018年上市。为了深入了解rVSV-ZEBOV疫苗,现主要从制备方法、药理学研究和作用机制等方面对该疫苗进行介绍。     

国内埃博拉病毒研究最新动态

对国内埃博拉病毒诊疗检测产品的近期研究成果及相关专利进行总结归纳,旨在为埃博拉病毒检测试剂及治疗药物的进一步开发提供参考。     

Development of therapeutics for treatment of Ebola virus infection

Ebola virus infection can cause Ebola virus disease (EVD). Patients usually show severe symptoms, and the fatality rate can reach up to 90%. No licensed medicine is available. In this review, development of therapeutics for treatment of Ebola virus infection and EVD will be discussed.     

Development of vaccines for prevention of Ebola virus infection

Ebola virus infection causes severe hemorrhagic fevers with high fatality rates up to 90% in humans, for which no effective treatment is currently available. The ongoing Ebola outbreak in West Africa that has caused over 14,000 human infections and over 5000 deaths underscores its serious threat to the public health. While licensed vaccines against Ebola virus infection are still not available, a number of vaccine approaches have been developed and shown to protect against lethal Ebola virus infection in animal models. This review aims to summarize the advancement of different strategies for Ebola vaccine development with a focus on the discussion of their protective efficacies and possible limitations. In addition, the development of animal models for efficacy evaluation of Ebola vaccines and the mechanism of immune protection against Ebola virus infection are also discussed.     

Epitopes of Naturally Acquired and Vaccine‐Induced Anti‐Ebola Virus Glycoprotein Antibodies in Single Amino Acid Resolution

The Ebola virus (EBOV) can cause severe infections in humans, leading to a fatal outcome in a high percentage of cases. Neutralizing antibodies against the EBOV surface glycoprotein (GP) can prevent infections, demonstrating a straightforward way for an efficient vaccination strategy. Meanwhile, many different anti‐EBOV antibodies have been identified, whereas the exact binding epitopes are often unknown. Here, the analysis of serum samples from an EBOV vaccine trial with the recombinant vesicular stomatitis virus‐Zaire ebolavirus (rVSV‐ZEBOV) and an Ebola virus disease survivor, using high‐density peptide arrays, is presented. In this proof‐of‐principle study, distinct IgG and IgM antibodies binding to different epitopes of EBOV GP is detected: By mapping the whole GP as overlapping peptide fragments, new epitopes and confirmed epitopes from the literature are found. Furthermore, the highly selective binding epitope of a neutralizing monoclonal anti‐EBOV GP antibody could be validated. This shows that peptide arrays can be a valuable tool to study the humoral immune response to vaccines in patients and to support Ebola vaccine development.     

埃博拉病毒疫苗研究进展

埃博拉病毒是一种可引起人和非人灵长类动物出血热传染病的最为致命的烈性病毒,致死率可达90%。2014年在西非爆发的埃博拉疫情引起了全世界的关注。疫苗接种是预防和控制传染病最为常规和有效的方法,尽管目前还没有正式获得批准上市的埃博拉病毒疫苗,但是已有多个尚处于研究阶段的疫苗在非人灵长类动物上取得了很好的保护效果,并有几个已进入临床Ⅰ期试验阶段,有望尽快用于本次埃博拉疫情的防控。本文对目前处于研究阶段的多个类型的埃博拉病毒疫苗进行了综述,为相关研究人员提供参考。