埃博拉病毒疫苗最新研究进展

埃博拉病毒(Ebola virus,EBOV)是引起人类和非人灵长类动物严重出血热的最危险病原体之一,1976年首次得到报道.2014年撒哈拉以南非洲暴发的EBOV病的病死率高达90％.研究表明EBOV灭活疫苗无效,但多个新型EBOV候选疫苗已在临床前试验中显示有效,其中部分已进入临床试验.这些新型疫苗包括病毒载体疫苗、病毒样颗粒疫苗和核酸疫苗.此文对EBOV疫苗的研究进展做一综述.     

Development of experimental and early investigational drugs for the treatment of Ebola virus infections

Introduction: Ebola virus (EBOV) causes severe hemorrhagic fever in humans, and due to the aggressive nature of infection it has been difficult to develop effective medical countermeasures. Total casualties from past outbreaks numbered fewer than 1500 cases, but EBOV unexpectedly emerged from Guinea in late 2013 and infected over 25,000 people in nine countries spanning Africa, Europe and North America. Concern among the public and authorities helped spark an unprecedented push to fast-track experimental drugs for clinical use.

Areas covered: The authors provide a historical timeline of the progress in developing a licensed post-exposure EBOV drug for use in humans. Furthermore, they summarize and discuss the published data with different in light of their potential to play a role during outbreak times.

Expert opinion: Monoclonal antibody-based therapy is able to reverse advanced EBOV disease, but the outbreak of an antigenically divergent filovirus would require the reformulation and possibly redevelopment of the most promising candidates. Immunocompetent small animal models have not yet been developed for screening drugs against other filoviruses aside from Ravn and Marburg virus, and thus the number of prophylactic and therapeutic candidates lag behind that of EBOV. There is an urgent need for the proactive development of drugs against other neglected pathogens before the next major outbreak.     

埃博拉病毒疫苗研究进展

埃博拉出血热是埃博拉病毒(Ebola virus,EBOV)引起的人类和非人灵长类动物急性出血性传染病,目前尚无治疗药物和疫苗获得批准.科研人员正在进行EBOV疫苗的研发,包括病毒样颗粒疫苗、DNA疫苗和病毒载体疫苗等.虽然这些疫苗的免疫机制各不相同,但部分疫苗在非人灵长类动物中能有效对抗EBOV,提示有望成功研制出EBOV疫苗.     

埃博拉病毒病的治疗及新药研究进展

埃博拉病毒是世界上最具威胁的病原体之一,2013年12月始于西非几内亚的埃博拉病毒病（Ebola virus disease,EVD）疫情,成为有记载以来最严重的一次暴发。由于对疫情的估计不足以及缺乏有效的治疗药物,本次疫情的防治效果并不乐观。美国FDA紧急批准了未经系统研究的ZMapp和TKM-Ebola用于埃博拉病毒病的治疗,但限于未知的疗效、安全性和产能的不足,意义有限。本文综述了现有的治疗埃博拉病毒病的方法以及新药的最新研究进展,方便相关人员了解此方面的信息。     

Development of a broad-spectrum antiviral with activity against Ebola virus

We report herein the identification of a small molecule therapeutic, FGI-106, which displays potent and broad-spectrum inhibition of lethal viral hemorrhagic fevers pathogens, including Ebola, Rift Valley and Dengue Fever viruses, in cell-based assays. Using mouse models of Ebola virus, we further demonstrate that FGI-106 can protect animals from an otherwise lethal infection when used either in a prophylactic or therapeutic setting. A single treatment, administered 1 day after infection, is sufficient to protect animals from lethal Ebola virus challenge. Cell-based assays also identified inhibitory activity against divergent virus families, which supports a hypothesis that FGI-106 interferes with a common pathway utilized by different viruses. These findings suggest FGI-106 may provide an opportunity for targeting viral diseases.     

术后早期炎性肠梗阻32例诊治体会

目的探讨术后早期炎性肠梗阻的临床特点和治疗。方法分析32例术后早期炎性肠梗阻患者的相关临床资料。结果32例患者全部治愈，平均治愈时间19d，无1例肠坏死。结论采用非手术疗法治疗术后早期炎性肠梗阻疗效较满意，值得进一步推广应用。     

The therapeutic potential of monoclonal antibodies against respiratory syncytial virus

Attempts to develop a vaccine against respiratory syncytial virus (RSV), the major cause of lower respiratory tract disease in infants and young children, have been unsuccessful. Passive immunisation with antibody to RSV has been found to be an effective alternative method for prophylaxis. The product currently in use for RSV passive immunisation, a preparation of purified human IgG containing virus-neutralising activity, requires monthly iv. infusions. Monoclonal antibodies (mAbs) are currently under development as an alternative means of treatment that would require lower doses. The first such mAb was recently approved for RSV prophylaxis in the USA. The mucosal delivery of antibodies is also effective and a mAb nose drop treatment for immunoprophylaxis is under development. The potential of passive immunisation for the treatment of existing RSV infections is not clear. Antibody treatment following infection clearly suppresses viral replication but it may not reduce disease once inflammatory processes have been initiated.     

Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein

Ebola virus (EBOV) infection leads to staggeringly high mortality rate. Effective and low-cost treatments are urgently needed to control frequent EBOV outbreaks in Africa. In this study, we report that a natural compound called berbamine hydrochloride strongly inhibits EBOV replication in vitro and in vivo. Our work further showed that berbamine hydrochloride acts by directly binding to the cleaved EBOV glycoprotein (GPcl), disrupting GPcl interaction with viral receptor Niemann-Pick C1, thus blocking the fusion of viral and cellular membranes. Our data support the probability of developing anti-EBOV small molecule drugs by targeting viral GPcl. More importantly, since berbamine hydrochloride has been used in clinic to treat leukopenia, it holds great promise of being quickly repurposed as an anti-EBOV drug.     

Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe

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Investigational drugs for the treatment of Zika virus infection: a preclinical and clinical update

ABSTRACT

Introduction: The Zika virus (ZIKV) infection results in severe neurological complications and has emerged as a threat to public health worldwide. No drugs or vaccines are available for use in the clinic and the need for novel and effective therapeutic agents is urgent.

Areas covered: This review describes the latest progress of antiviral development for the treatment of ZIKV infection; it primarily focuses on the literature describing 20 potential anti-ZIKV drugs/agents currently being tested in vivo or in clinical trials. The paper also discusses the need for novel ZIKV inhibitors and the critical issues for successful antiviral drug development.

Expert opinion: So far, 20 compounds have been tested in vivo and three in the clinical trials; progressing these compounds to the clinic is a challenge. Novel ZIKV inhibitors that target virus or host factors are urgently needed. Knowledge-driven drug repurposing, structure-based discovery, RNA interference, long noncoding RNAs, miRNAs, and peptide inhibitors may pave the way for the discovery of such novel agents.     

肝病患者1913例中庚型肝炎病毒感染状况的临床分析

目的　了解庚型肝炎病毒 (HGV)在各种类型病毒性肝炎中的感染状况 ,对 HGV感染的病例进行临床分析。方法　对 1913例不同临床类型的住院病人进行回顾性分析。结果　共检出抗 -HGV阳性 15 7例(8.2 1% ) ,其中单独抗 -HGV阳性者 3 6例 (1.88% ) ,与其他各型肝炎病毒均有重叠 /混合感染 ,共检出 12 1例(6.3 3 % )。在感染病例中以中青年为主 (5 9.2 4% ) ,肝癌患者中 HGV的感染率 (3 3 .3 3 % )明显高于其他组 (P<0 .0 0 5 )。结论　 HGV病毒可与其他各型肝炎病毒重叠 /混合感染 ,也可单独存在 ,可致各种肝炎、肝硬化 ,甚至可能引起肝癌     

早期干预对足月小样儿神经行为及智能发育影响的临床研究

目的 探讨早期综合干预对足月小样儿神经发育的临床干预效果。方法 选取2017年10月至2018年6月安徽省妇幼保健院儿保科就诊的60例足月小样儿,按随机数字法分为医院干预组（30例）与家庭干预组（30例）,同期选取30例参加体检的足月非小样儿作为对照组。医院干预组采用医院干预模式,家庭干预组采用家庭干预模式。对比分析不同干预模式下小儿在不同发育时期的运动量表（PDI）评分和智力量表（MDI）评分情况。结果 出生后第42天时,对照组PDI和MDI评分分别为（80.20±13.93）分、（82.20±12.36）分,均高于医院干预组及家庭干预组,差异有统计学意义（P<0.05）;出生后12个月,医院干预组患儿PDI和MDI评分分别为（91.47±11.01）分、（95.37±11.66）分,接近对照组,差异无统计学意义（P>0.05）,但高于家庭干预组,差异有统计学意义（P<0.05）。重复测量方差分析结果显示,医院干预组PDI和MDI评分均高于家庭干预组,且随着干预时间延长,医院干预组两项评分增加幅度最大。结论 早期综合干预对足月小样儿神经行为及智能发育有明显的促进作用。     

乙型肝炎病毒前S1抗原检测的临床应用

目的 探讨乙型肝炎病毒前S1( PreSl)抗原检测在乙型肝炎诊断中的临床意义。方法 采用ELISA检测HBV血清标志物,取其中阳性标本254份,并按不同模式分为三组,分别检测各组乙肝前Sl抗原、HBV DNA和ALT并进行比较分析。结果 前S1抗原和HBV-DNA在HbsAg(+)HBeAg(+)HBcAb(+)的检...     

早产儿早期异常神经行为变化的临床研究

目的探讨早产儿早期异常神经行为动态变化情况。方法将269例早产儿纠正胎龄从1、2、4、6个月分4个年龄段分别做52项神经行为检查,重点记录视听反应、头部控制、肌张力、神经反射及异常姿势的异常概率,并与同期出生的270例正常足月儿做比较。结果早产儿早期神经行为异常表现随月龄增长有下降趋势,越早越明显,其早期神经行为异常主要集中在视听反应、头部控制、肌张力变化三方面,1、2、4个月与正常组相比差异有统计学意义(P<0.05),随月龄增长至4、6个月,则以头部控制、肌张力、异常姿势的异常为主,与正常组相比差异有统计学意义(P<0.05)。结论早产儿早期异常神经行为处于动态变化中,定期追踪检查有助于把握干预时机,及时纠正异常的神经行为。     

Drugs in early clinical development for the treatment of female sexual dysfunction

Introduction: There is growing recognition of female sexual dysfunction (FSD) as an important women’s health concern. Despite an increased awareness of the pathophysiologic components to FSD, currently, there are no drugs approved for the most common sexual complaint in women–decreased sexual desire. In response to an overwhelming demand for therapy for FSD, several drugs are undergoing development and testing.

Areas covered: The aim of this paper is to provide the latest data on pharmacological treatments for FSD currently in Phase I and II clinical trials. These include topical alprostadil, bremelanotide (BMT), intranasal testosterone (TBS-2), intravaginal dehydroepiandrosterone (DHEA), sublingual testosterone with sildenafil, apomorphine (APO), bupropprion and trazodone. It should be noted that the definitions of FSD have recently been revised in the diagnostic and statistical manual for mental disorders (DSM) 5, with merging of hypoactive sexual desire disorder (HSDD) and female sexual arousal disorder (FSAD) into female sexual interest/arousal disorder (FSIAD). However, it is noted that the majority of clinical trials discussed in this paper use the DSM IV-R diagnoses of HSDD and FSAD.

Expert opinion: Medications in early phase trials show promise for the treatment of FSD. These therapies focus on treating many possible causes of FSD. Concerns over gender bias within the FDA need to be resolved given the need for new treatment options for FSD.     

The design and development of drugs acting against the smallpox virus

The eradication of smallpox was announced by the WHO in 1980. However, smallpox has not totally disappeared from people's minds because of its potential use as a biological weapon. Further outbreaks of smallpox would, needless to say, be devastating in a population, which has little or no immune defence against the virus. The real concerns come from the fact that the previously used vaccine would not be tolerated today by a number of patients and, more worryingly, there are no approved antiviral drugs against smallpox. This review is focused on the antiviral research, which has been stimulated to deliver potent inhibitors of the replication of the causative agent of smallpox, variola virus.     

低剂量螺旋CT扫描联合血清p53抗体检测在肺癌早期诊断中的临床价值

目的 研究低剂量螺旋CT扫描联合血清p53抗体检测诊断早期肺癌的临床价值. 方法 选择300例符合标准的受检者按不同检查方法分为实验组和对照组,每组各150例.实验组150例患者行低剂量螺旋CT扫描联合血清p53抗体检测,对照组150例患者行胸部X线正侧位检查,对两组患者检查结果阳性者进一步病理确诊,比较两种不同方法可疑肺癌的检出率及确诊肺癌的准确率.结果 实验组可疑肺癌的检出率及确诊肺癌的准确率分别为11.33％、88.2％,明显高于对照组的6.67％、70.0％ （P＜0.05）.结论 低剂量螺旋CT扫描联合血清p53抗体检测用于肺癌早期筛查时,更加敏感,作用更大.     

乙型肝炎病毒外膜大蛋白检测的临床意义

目的探讨乙型肝炎病毒外膜大蛋白（HBV—LP）与乙型肝炎病毒脱氧核糖核酸（HBV—DNA）的相关性,动态检测俩项指标,分析其在诊断乙型肝炎和临床治疗,妒的意义。方法采用酶联免疫吸附试验和实时荧光定量聚合酶链反应技术对230例乙型肝炎患者血清标本进行HBV—LP和HBV-DNA平行检测。结果乙型肝炎病毒感染患者血清HBV—LP含量与HBV—DNA拷贝数间呈正相关（r=0．84,P〈0．01）,230例乙肝病毒感染患者血清标本中,HBV-LP阳性率为84.78％,HBV-DNA阳性率为84．35％,两者差异无统计学意义（P〉0．05）。55例HBeAg阴性血清标本中,HBV—LP与HBV-DNA的阳性检出率分别为63．63％（35／55）、58．18％（32／55）,两者差异无统计学意义（P〉0．05）。HBV—DNA阳性194例中,HBV—LP阳性率（82．47％）明显高于HBeAg阳性率（52．06％）（x2=80：3,P〈0．01）。结论HBV—LP及HBV-DNA是判断乙型肝炎病毒感染患者体内病毒复制程度的重要指标,尤其是HBeAg阴性患者体内病毒复制及预后判断有价值的血清学检测指标,为临床诊断及治疗提供可靠的实验室数据。     

The early preclinical and clinical development of ganaplacide (KAF156), a novel antimalarial compound

ABSTRACT

Introduction: Ganaplacide (previously known as KAF156) is a novel antimalarial compound part of the imidazolopiperazine family.

Areas covered: At the time of writing, a total of eight studies addressing its preclinical and clinical development have been published on this compound, which is currently in phase 2 of clinical development, alongside lumefantrine in a novel soluble formulation as combination partner. This review provides an overview and interpretation of the published pre-clinical and clinical data of this possible next-generation antimalarial drug.

Expert opinion: In the search for a ‘magic bullet’ in malaria therapy and prophylaxis facilitating single encounter radical cure and prophylaxis, ganaplacide demonstrates some promising properties toward this ultimate goal. The available data suggest that ganaplacide exerts multi-stage antimalarial activity, and that its pharmacokinetic profile potentially allows for a simplified dosing regimen compared to that of existing antimalarial drug combinations. The first in-patient results demonstrate promising single-dose antimalarial activity, and no serious in-human safety and tolerability concerns have been reported to date.