药学学报, 2018, 53(5): 735-742
引用本文:
张晓雨, 唐克, 郭家梅, 陈勍, 郭颖. 沙粒病毒进入抑制剂体外药效学评价模型的建立[J]. 药学学报, 2018, 53(5): 735-742.
ZHANG Xiao-yu, TANG Ke, GUO Jia-mei, CHEN Qing, GUO Ying. Establishment of a cell-based evaluation system for arenavirus entry inhibitor[J]. Acta Pharmaceutica Sinica, 2018, 53(5): 735-742.

沙粒病毒进入抑制剂体外药效学评价模型的建立
张晓雨, 唐克, 郭家梅, 陈勍, 郭颖
中国医学科学院、北京协和医学院药物研究所, 新药作用机制研究与药效评价北京市重点实验室, 北京 100050
摘要:
沙粒病毒是一类有囊膜的RNA病毒。以哺乳动物为宿主的沙粒病毒(mammarenavirus)中,有9种可致人疾病,其中8种可致人出血热。拉沙病毒(Lassa virus,LASV)感染人所致拉沙出血热(Lassa hemorrhagic fever)流行范围广,有引发疾病大流行的可能,因此拉沙病毒被列为第一类病原微生物。目前针对沙粒病毒的疫苗和药物极为有限。本研究应用重组病毒技术,以HIV-1为核心,共构建了以9种沙粒病毒外壳蛋白包裹的重组病毒(arenavirus-GP/HIV-luc),在考察了它们对17株人、猴、鼠及蝙蝠的不同组织来源细胞进入水平的基础上,建立了沙粒病毒进入抑制剂药理活性评价模型,并用工具药验证。本研究建立的重组沙粒病毒进入抑制剂体外药效学评价模型特异性好,安全性高,可在生物安全二级(BSL-2)实验室进行实验,可为抗沙粒病毒药物和疫苗的活性评价提供技术平台,促进针对沙粒病毒出血热的药物及疫苗的研发。
关键词:   
Establishment of a cell-based evaluation system for arenavirus entry inhibitor
ZHANG Xiao-yu, TANG Ke, GUO Jia-mei, CHEN Qing, GUO Ying
Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Abstract:
Arenaviruses are enveloped RNA viruses. The genus mammarenavirus contains nine members that are known to be human pathogens, and eight of them cause human hemorrhagic fever. Lassa hemorrhagic fever, caused by Lassa virus (LASV) infection, is the most prevalent arenavirus hemorrhagic fever with potential to cause major epidemics. LASV belongs to category A agents, and biosafety level-4 (BSL-4) facility is required for live virus experiments. Currently there are few specific treatments available for arenavirus diseases. Here, we established efficient cell-based pseudovirus infection models using an HIV-1 core (pNL4-3.Luc.R-E-) packed with arenavirus glycoproteins. Nine recombinant arenaviruses (arenavirus-GP/HIV-luc) were generated, and 17 cell lines were tested for susceptibilities to these viruses. These pseudovirus infection models were further validated by known arenavirus entry inhibitors. The models are safe and specific to pseudovirus infection, which are readily used for pharmacodynamic evaluation of arenavirus entry inhibitors in BSL-2 laboratory. The models will facilitate screening of the anti-arenavirus drugs and vaccines.
Key words:   
收稿日期: 2018-01-08
DOI: 10.16438/j.0513-4870.2018-0028
基金项目: 国家科技重大专项“重大新药创制”(2015ZX09102-023-004);北京市科委全市成果转化统筹基金(Z151100000115008);中国医学科学院医学与健康科技创新工程(2016-I2M-1-014).
通讯作者: 郭颖,Tel:86-10-63161716,E-mail:yingguo6@imm.ac.cn
Email: yingguo6@imm.ac.cn
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