呼吸道合胞病毒化学治疗药物的研究进展

到目前为止，对呼吸道合胞病毒(RSV)感染的研究已经有了一定进展，但是尚无特异有效的治疗和预防方案。目前唯一允许用于化学疗法的药物仍是利巴韦林，因此人们加大力量开发研制新的有效防治RSV感染的药物。主要包括两方面：(1)人工合成的具有抗病毒活性的化合物；(2)源于天然药物的抗病毒活性物质。本文综述了近年来国内外人工合成的各种类型的抗病毒因子的结构特点、抗病毒效果和作用机制，以及已经从天然药物中分离出的各种有效的抗RSV成分。     

夏桑菊抗呼吸道合胞病毒的实验研究

目的 评价夏桑菊抗呼吸道合胞病毒(RSV)的疗效.方法 以病毒唑为对照,通过体外观察病毒致细胞病变效应(CPE)、病毒滴度、抗病毒指数;在体内观察其对染毒小鼠的死亡保护作用以及对小鼠心、脑、肺内病毒增殖的影响,从而判定夏桑菊抗RSV作用.结果 夏桑菊能抑制RSV的增殖,其有效浓度为544.59 μg/ml,并显示出病毒的感染性滴度随药物浓度的增加而下降;治疗RSV感染鼠结果 发现夏桑菊对RSV感染鼠有保护作用,10 g/(kg*d)时,RSV感染鼠的存活率为50%,平均存活天数为(10.9±2.3)d,随着药物剂量增加,疗效增强,该药物还能降低组织内病毒滴度,阻止体内病毒复制,抗RSV作用类似于同剂量的病毒唑.结论 夏桑菊是一种抗呼吸道合胞病毒的有效药物.     

呼吸道合胞病毒抑制剂研究新进展

呼吸道合胞病毒(RSV)是引起婴幼儿、老年人和免疫功能低下者呼吸道感染的主要病原体。目前,利巴韦林和人源化单克隆抗体帕利珠常用于RSV引发的下呼吸道感染,但由于它们的疗效、经济性与安全性等问题限制了其临床应用。因此需要开发新型的RSV抑制剂来满足临床预治的需求。本文精选典型研究案例,从药物化学的角度综述了不同靶点RSV抑制剂的研究进展。     

干扰素、病毒唑抗呼吸道合胞病毒的体外观察

目的　观察重组人干扰素、病毒唑单独及联合体外抗呼吸道合胞病毒(RSV)的效果。方法　细胞病变抑制法,即测定药物单独及联合应用对RSV所致细胞病变的抑制作用。结果　干扰素浓度≥5　IU     

双黄连口服液抗呼吸道合胞病毒的实验研究

目的:评价双黄连口服液抗呼吸道合胞病毒(RSV)的活性。方法:以病毒唑为对照,通过体外观察病毒致细胞病变效应(CPE)、病毒滴度、抗病毒指数,在体内观察其对染毒小鼠的死亡保护作用,以及对小鼠心、脑、肺内病毒增殖的影响,从而判定双黄连口服液抗RSV作用。结果:双黄连口服液能抑制RSV的增殖,其有效浓度为12ug/mL,并显示出病毒的感染性滴度随药物浓度的增加而下降;治疗RSV感染鼠结果发现,双黄连口服液对RSV感染鼠有保护作用,6.7g.k-g 1.d-1时,RSV感染鼠的存活率为75%,平均存活天数为(12.9±2.8)d,随着药物剂量增加,疗效增强;该口服液还能降低组织内病毒滴度,阻止体内病毒复制,抗RSV作用类似于同剂量的病毒唑。结论:双黄连口服液是一种有效的抗RSV中药复方制剂。     

呼吸道合胞病毒疫苗研究进展

本文介绍了近年来呼吸道合胞病毒（ＲＳＶ）疫苗的研究状况。重组亚单位疫苗安全，但免疫原性有待提高；减毒活疫苗能诱导全面免疫应答，若合理减毒，似可成为有希望的候选疫苗。     

抗呼吸道合胞病毒单克隆抗体

呼吸道合胞病毒是造成婴幼儿下呼吸道感染的常见原因，目前尚无有效的自动免疫制剂，本文介绍了两种被动免疫制剂，并就它们的应用范围和各自的优缺点作了说明。     

呼吸道合胞病毒疫苗的研究进展

人呼吸道合胞病毒(HRSV)是一个世界范围内的婴幼儿最常见的严重呼吸道感染的病原体，它约占儿科呼吸道疾病住院人数的四分之一，全球每年有近四百万儿童受其感染。近年来认为它也是感染成人的一个重要病原体，由于老年人和免疫受抑被感染后不能获得有效的保护性免疫反应，因而可反复出现     

呼吸道合胞病毒疫苗的研究进展

人呼吸道合胞病毒(HRSV)是一个世界范围内的婴幼儿最常见的严重呼吸道感染的病原体,它约占儿科呼吸道疾病住院人数的四分之一,全球每年有近四百万儿童受其感染[1].近年来认为它也是感染成人的一个重要病原体,由于老年人和免疫受抑者[2]被感染后不能获得有效的保护性免疫反应,因而可反复出现HRSV感染[1].现在,对HRSV的结构及功能的研究已取得了明显的成果,HRSV疫苗的研究也一直在进行中,有几种候选疫苗已处于临床试验阶段.现就HRSV疫苗的研究进展作一综述.     

抗呼吸道合胞病毒药物专利技术分析

呼吸道合胞病毒（简称RSV）是引起2岁以下儿童急性下呼吸道感染最常见与最重要的病原,属于国内外的研发热点。本文以抗呼吸道合胞病毒的专利申请文献为基础,对其技术发展现状、国内外专利申请态势、技术分布、重点申请人等情况进行梳理分析,表明欧美发达国家在抗呼吸道合胞病毒药物研究中处于绝对领先地位,我国近年来处于快速发展阶段。     

儿童呼吸道合胞病毒感染的药物治疗研究进展及其预防策略

呼吸道合胞病毒是引起儿童下呼吸道感染的主要原因,目前临床主要的治疗措施为对症支持治疗,尚缺乏特异性抗病毒药物和安全有效的预防措施。近年来,多种新型药物已经进入了临床研究后阶段,部分药物已上市。综述了治疗呼吸道合胞病毒的早期和新型抗病毒药物的研究进展以及呼吸道合胞病毒主动、被动免疫预防策略,旨在提高临床医生对儿童呼吸道合胞病毒防治策略的认识。     

败酱草多糖体外抗呼吸道合胞病毒作用的研究

目的: 了解败酱草多糖(AP4)对呼吸道合胞病毒的体外抑制作用.方法: 经提取、沉淀、离心、大孔吸附树脂两次层析后,得败酱草抗病毒多糖AP4.通过细胞培养法检测呼吸道合胞病毒对Hela细胞的致病变作用及AP4对呼吸道合胞病毒感染Hela细胞的治疗作用.结果: AP4半数中毒浓度(TC50)为11.07mg/ml,抑制呼吸道合胞病毒的半数有效浓度(EC50)为0.097mg/ml,治疗指数(TI)为114;病毒唑半数中毒浓度(TC50)2.087 mg/ml,抑制呼吸道合胞病毒的半数有效浓度(EC50)为0.0385 mg/ml,治疗指数(TI)为54.结论: 败酱草抗病毒有效部位AP4在Hela细胞中对呼吸道合胞病毒有明显的抑制作用.     

中药抗呼吸道合胞病毒实验研究进展

中药具有高效低毒的特点,分别从抗呼吸道合胞病毒(RSV)复方和单味中药提取物2个方面,总结中药对RSV的实验抑菌作用及其作用机制,期待为临床治疗提供理论依据,并为进一步挖掘和深入研究中药抗病毒成分提供新的思路。同时指出了单味中药提取物虽然可以较为清晰地说明治疗机制和作用靶点,但目前多数尚停留在物质分析、鉴定和少数动物细胞实验阶段。     

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.     

呼吸道合胞病毒的治疗药物研发进展

呼吸道合胞病毒(RSV)是婴幼儿、老年人和免疫功能低下者诱发下呼吸道感染的主要原因。RSV引起严重的呼吸系统疾病,与长期喘息和后期哮喘风险增加有关。虽然RSV疫苗的开发已经有50多年,仍然没有批准上市的疫苗,对于预防和治疗RSV感染的疫苗和有效治疗药物尚未满足临床需求。帕利珠单抗和利巴韦林目前可用于RSV感染的预防和治疗,但不完全有效。因此需要针对RSV的预防和治疗提出新的疗法,用于满足临床医疗需求。近10年来,新抗病毒药物和单克隆抗体的研发,已经显示出对RSV治疗的临床应用前景,并且可能在未来几年陆续上市。尽管RSV融合蛋白(F蛋白)已成为小分子抑制剂和单克隆抗体最受欢迎的靶点,但靶向病毒其他蛋白质的新方法也得到了发展。同时针对逃逸株,可能会采用联合用药,用于RSV病毒的治疗。对处于不同临床研发阶段的抗RSV病毒药物和单克隆抗体进行了综述。     

An update on respiratory syncytial virus antiviral agents

Respiratory syncytial virus (RSV), the most common cause of lower respiratory tract disease in infants and young children, is a ubiquitous respiratory pathogen, infecting or reinfecting much of the population every year and causing severe, sometimes fatal disease in high-risk populations of infants and adults, particularly in developing countries. Spurred by the medical and economic burdens of RSV disease and enticed by the economic potential of therapeutic drugs, particularly in the absence to date of a safe and effective RSV vaccine, scientists in many industrial, academic and government laboratories have developed a wide variety of candidate RSV antiviral agents. Most of these have been screened thus far only in cell culture, a few in animal models. Aside from ribavirin, however, none has proven effective in therapeutic clinical trials and even ribavirin usage has declined precipitously in recent years due to concerns over efficacy, safety, ease of use and cost. All of the antiviral compounds discussed in this review were evaluated primarily for their ability to reduce viral load, with little or no attention paid to the role of host inflammation in the pathogenesis of RSV disease. Recent research has highlighted the prominent role of inflammatory mediators and an increasing number of reports suggest that a therapeutic strategy that combines antiviral and anti-inflammatory components will be the most effective way of treating RSV disease.     

Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate

A number of different viruses including respiratory syncytial virus (RSV) initiate infection of cells by binding to cell surface glycosaminoglycans and sulfated oligo- and polysaccharide mimetics of these receptors exhibit potent antiviral activity in cultured cells. We investigated whether the introduction of different lipophilic groups to the reducing end of sulfated oligosaccharides would modulate their anti-RSV activity. Our results demonstrate that the cholestanol-conjugated tetrasaccharide (PG545) exhibited ∼5- to 16-fold enhanced anti-RSV activity in cultured cells compared with unmodified sulfated oligosaccharides. Furthermore, PG545 displayed virus-inactivating (virucidal) activity, a feature absent in sulfated oligosaccharides. To inhibit RSV infectivity PG545 had to be present during the initial steps of viral infection of cells. The anti-RSV activity of PG545 was due to both partial inhibition of the virus attachment to cells and a more profound interference with some post-attachment steps as PG545 efficiently neutralized infectivity of the cell-adsorbed virus. The anti-RSV activity of PG545 was reduced when tested in the presence of human nasal secretions. Serial passages of RSV in the presence of increasing concentrations of PG545 selected for weakly resistant viral variants that comprised the F168S and the P180S amino acid substitutions in the viral G protein. Altogether we identified a novel and potent inhibitor of RSV, which unlike sulfated oligo- and polysaccharide compounds, could irreversibly inactivate RSV infectivity.     

注射用银黄体外抗呼吸道合胞病毒

目的:研究注射用银黄对呼吸道合胞病毒的体外抑制作用。方法:采用细胞培养技术,通过银黄直接抗病毒,病毒感染细胞同时使用银黄,先使用银黄再感染病毒3种给药方法,利用生物显微镜观察人喉癌细胞(Hep-2)和人宫颈癌细胞(Hela)发生病变的情况及观察实验组与病毒对照组病毒感染的滴度。结果:注射用银黄在Hep-2和Hela细胞上对呼吸道合胞病毒均有明显的抗病毒作用,注射用银黄对病毒的最小有效浓度(M IC)为0.016 g.L-1,而且毒性低,最大无毒浓度(TDO)为1.6 g.L-1,治疗指数(TI)为100。结论:体外实验注射用银黄对呼吸道合胞病毒具有抑制和直接杀灭的特异性。     

Effectiveness of drug therapies to treat or prevent respiratory syncytial virus infection-related morbidity

Respiratory syncytial virus (RSV) infection causes a huge burden to the health service, as it results in a large number of in-patient days each year and increases the risk of asthma in childhood. In the acute phase, therapy is supportive as bronchodilators and corticosteroids have resulted, at best, only in short-term benefits; promising treatments for ventilated patients, such as exogenous surfactant, require further testing. Passive immunoprophylaxis reduces hospital admission in high risk groups. In the prevention of chronic respiratory morbidity following RSV infection, however, studies are needed to determine whether immunoprophylaxis will have a useful role and to identify which drug treatment will be most cost-effective.