GS-5806抑制呼吸道合胞病毒融合蛋白从融合前构象到融合后构象的变化。
GS-5806 inhibits pre- to postfusion conformational changes of the respiratory syncytial virus fusion protein.
作者信息
Samuel Dharmaraj, Xing Weimei, Niedziela-Majka Anita, Wong Jinny S, Hung Magdeleine, Brendza Katherine M, Perron Michel, Jordan Robert, Sperandio David, Liu Xiaohong, Mackman Richard, Sakowicz Roman
机构信息
Gilead Sciences, Inc., Foster City, California, USA
Gilead Sciences, Inc., Foster City, California, USA.
出版信息
Antimicrob Agents Chemother. 2015 Nov;59(11):7109-12. doi: 10.1128/AAC.00761-15. Epub 2015 Aug 31.
Abstract
GS-5806 is a small-molecule inhibitor of human respiratory syncytial virus fusion protein-mediated viral entry. During viral entry, the fusion protein undergoes major conformational changes, resulting in fusion of the viral envelope with the host cell membrane. This process is reproduced in vitro using a purified, truncated respiratory syncytial virus (RSV) fusion protein. GS-5806 blocked these conformational changes, suggesting a possible mechanism for antiviral activity.
摘要
GS-5806是一种人呼吸道合胞病毒融合蛋白介导的病毒进入的小分子抑制剂。在病毒进入过程中，融合蛋白会发生重大构象变化，导致病毒包膜与宿主细胞膜融合。使用纯化的、截短的呼吸道合胞病毒（RSV）融合蛋白在体外重现了这一过程。GS-5806阻断了这些构象变化，提示了一种可能的抗病毒活性机制。
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本文引用的文献
1
GS-5806 Inhibits a Broad Range of Respiratory Syncytial Virus Clinical Isolates by Blocking the Virus-Cell Fusion Process.GS-5806通过阻断病毒-细胞融合过程抑制多种呼吸道合胞病毒临床分离株。
Antimicrob Agents Chemother. 2015 Dec 14;60(3):1264-73. doi: 10.1128/AAC.01497-15.
2
Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study.发现一种口服呼吸道合胞病毒（RSV）融合抑制剂（GS-5806），并在人体 RSV 挑战研究中得到临床概念验证。
J Med Chem. 2015 Feb 26;58(4):1630-43. doi: 10.1021/jm5017768. Epub 2015 Jan 27.
3
Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors.呼吸道合胞病毒对结构多样的进入抑制剂的交叉耐药机制。
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3441-9. doi: 10.1073/pnas.1405198111. Epub 2014 Aug 4.
4
Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age.小于 24 月龄儿童因呼吸道合胞病毒导致的住院治疗。
Pediatrics. 2013 Aug;132(2):e341-8. doi: 10.1542/peds.2013-0303. Epub 2013 Jul 22.
5
High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections.成人因呼吸道合胞病毒感染住院的发病率和死亡率高。
Clin Infect Dis. 2013 Oct;57(8):1069-77. doi: 10.1093/cid/cit471. Epub 2013 Jul 21.
6
Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults.老年人因呼吸道合胞病毒、人偏肺病毒和流感病毒而住院的比率。
J Infect Dis. 2012 Jul 1;206(1):56-62. doi: 10.1093/infdis/jis309. Epub 2012 Apr 23.
7
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Pediatr Infect Dis J. 2012 Jan;31(1):5-9. doi: 10.1097/INF.0b013e31822e68e6.
8
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J Virol. 2011 Apr;85(8):3968-77. doi: 10.1128/JVI.01813-10. Epub 2011 Feb 9.
9
Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis.全球儿童因呼吸道合胞病毒导致的急性下呼吸道感染负担：系统评价和荟萃分析。
Lancet. 2010 May 1;375(9725):1545-55. doi: 10.1016/S0140-6736(10)60206-1.
10
Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein.强效六螺旋束形成小分子抑制剂的结合需要与 RSV 融合蛋白的七个重复序列都相互作用。
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):308-13. doi: 10.1073/pnas.0910108106. Epub 2009 Dec 4.
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