A high-throughput screening strategy to overcome virus instability.

A high-throughput screening strategy to overcome virus instability.
复制标题

克服病毒不稳定性的高通量筛选策略。

DOI:
10.1089/adt.2010.0298
复制
发表时间:
2011
影响因子:
1.8
通讯作者:
White,ELucile
White,ELucile
中科院分区:
医学4区
文献类型:
--
作者:
Rasmussen,Lynn;Maddox,Clinton;Moore,BlakeP;Severson,William;White,ELucile

文献摘要

参考文献

被引文献

相似文献

呼吸道合胞病毒(RSV)是一种广泛分布的病原体,可在儿童、老年人和免疫功能低下的个体中引起严重疾病。疫苗开发和药物发现都受到病毒本身固有的不稳定性的阻碍。药物发现的努力取得了有限的成功,至少部分是由于缺乏足够强大的高通量筛选的抗病毒测定。纯化病毒的不稳定性长期以来一直被认为是RSV研究中的问题,并且一直是产生基于病毒的筛选测定的主要障碍。使用冷冻的RSV感染的细胞作为感染材料的来源,我们已经克服了病毒不稳定性的问题,并验证了基于细胞的高通量筛选试验,以筛选抑制剂的RSV诱导的细胞病变效应。在基于病毒的筛选中,使用1,280种被鉴定为对RSV(Long株)具有潜在活性的化合物对该测定法进行了验证。迄今为止,已经在几个月内筛选了超过30万种化合物,细胞或病毒对照的变异性最小。长期试验稳定性研究仍在进行中。
Respiratory syncytial virus (RSV) is a widely distributed pathogen that causes severe disease in children, the elderly, and immunocompromised individuals. Both vaccine development and drug discovery have been hampered by the inherent instability of the virus itself. Drug discovery efforts have had limited success due, at least in part, to the lack of an antiviral assay robust enough for high-throughput screening. Instability of the purified virus has long been recognized as a problem in RSV research and has been a major hurdle to producing a virus-based screening assay. Using frozen RSV-infected cells as the source of infectious material, we have overcome the problem of virus instability and validated a cell-based high-throughput screening assay to screen for inhibitors of RSV-induced cytopathic effect. The assay was validated with 1,280 compounds identified as potentially active against RSV (Long strain) in a virus-based screen. To date over 300,000 compounds have been screened over several months with minimal variability in cell or virus controls. Long-term assay stability studies are still in progress.
冷冻保存的细胞有利于基于细胞的药物发现。
DOI: 10.1016/j.drudis.2007.05.008
发表时间: 2007
影响因子: 7.4
作者:
G. Zaman;J. D. de Roos;M. Blomenröhr;C. V. van Koppen;J. Oosterom
通讯作者: J. Oosterom
呼吸道合胞病毒的生长特性。
DOI: 10.4049/jimmunol.88.5.581
发表时间: 1962
影响因子: 4.4
作者:
W. S. Jordan
通讯作者: W. S. Jordan
DOI: 10.1056/nejm199107043250105
发表时间: 1991-07-04
影响因子: 158.5
作者:
SMITH, DW;FRANKEL, LR;PROBER, CG
通讯作者: PROBER, CG
杆状病毒 GP64 蛋白的掺入增强了人呼吸道合胞病毒的稳定性。
DOI: 10.1016/j.vaccine.2007.04.066
发表时间: 2007
期刊: Vaccine
影响因子: 5.5
作者:
Sastre,Patricia;Oomens,AntoniusGP;Wertz,GailW
通讯作者: Wertz,GailW