A small-molecule fusion inhibitor of influenza virus is orally active in mice

doi:10.1126/science.aar6221

GSTDTAP > 地球科学

DOI	10.1126/science.aar6221
	A small-molecule fusion inhibitor of influenza virus is orally active in mice
	van Dongen, Maria J. P.1,2; Kadam, Rameshwar U.3; Juraszek, Jarek 1; Lawson, Edward 4; Brandenburg, Boerries 1,5; Schmitz, Frederike 1; Schepens, Wim B. G.2; Stoops, Bart 2; van Diepen, Harry A.1; Jongeneelen, Mandy 1,5; Tang, Chan 1,5; Vermond, Jan 1; Real, Alida van Eijgen-Obregoso 1; Blokland, Sven 1,5; Garg, Divita 6; Yu, Wenli 3; Goutier, Wouter 1; Lanckacker, Ellen 7; Klap, Jaco M.1; Peeters, Danielle C. G.2; Wu, Jin 7; Buyck, Christophe 2; Jonckers, Tim H. M.7; Roymans, Dirk 7; Roevens, Peter 2; Vogels, Ronald 1,5; Koudstaal, Wouter 1,10; Friesen, Robert H. E.1,11; Raboisson, Pierre 7,12; Dhanak, Dashyant 2,4,13; Goudsmit, Jaap 1,8; Wilson, Ian A.3,9
	2019-03-08
发表期刊	SCIENCE
ISSN	0036-8075
EISSN	1095-9203
出版年	2019
卷号	363 期号:6431 页码:1056-+
文章类型	Article
语种	英语
国家	Netherlands; Belgium; USA; Spain
英文摘要	Recent characterization of broadly neutralizing antibodies (bnAbs) against influenza virus identified the conserved hemagglutinin (HA) stem as a target for development of universal vaccines and therapeutics. Although several stem bnAbs are being evaluated in clinical trials, antibodies are generally unsuited for oral delivery. Guided by structural knowledge of the interactions and mechanism of anti-stem bnAb CR6261, we selected and optimized small molecules that mimic the bnAb functionality. Our lead compound neutralizes influenza A group 1 viruses by inhibiting HA-mediated fusion in vitro, protects mice against lethal and sublethal influenza challenge after oral administration, and effectively neutralizes virus infection in reconstituted three-dimensional cell culture of fully differentiated human bronchial epithelial cells. Cocrystal structures with H1 and H5 HAs reveal that the lead compound recapitulates the bnAb hotspot interactions.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000460750100035
WOS关键词	BROADLY NEUTRALIZING ANTIBODIES ; HEMAGGLUTININ STRUCTURES ; STRUCTURAL BASIS ; STEM ; PROTEINS ; EPITOPES ; IMMUNITY ; BINDING ; DESIGN ; CELLS
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/200929
专题	地球科学资源环境科学气候变化
作者单位	1.Janssen Pharmaceut Companies Johnson & Johnson, Janssen Prevent Ctr, Archimedesweg 6, Leiden, Netherlands; 2.Janssen Res & Dev, Discovery Sci, Turnhoutseweg 30, Beerse, Belgium; 3.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA; 4.Janssen Res & Dev, Discovery Sci, 1400 McKean Rd, Spring House, PA USA; 5.Janssen Res & Dev, Janssen Infect Dis & Vaccines, Archimedesweg 4-6, Leiden, Netherlands; 6.Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA; 7.Janssen Res & Discovery, Janssen Infect Dis & Vaccines, Turnhoutseweg 30, Beerse, Belgium; 8.Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA; 9.Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA; 10.Lucid Biomed Consulting, Calle Emir 11, Granada, Spain; 11.Kiadis Pharma, Paasheuvelweg 25A, Amsterdam, Netherlands; 12.Bio Incubator Leuven NV, Aligos Bvba, Gaston Geenslaan 1, Leuven, Belgium; 13.Incyte Corp, 1801 Augustine Cut Off, Wilmington, DE USA
推荐引用方式 GB/T 7714	van Dongen, Maria J. P.,Kadam, Rameshwar U.,Juraszek, Jarek,et al. A small-molecule fusion inhibitor of influenza virus is orally active in mice[J]. SCIENCE,2019,363(6431):1056-+.
APA	van Dongen, Maria J. P..,Kadam, Rameshwar U..,Juraszek, Jarek.,Lawson, Edward.,Brandenburg, Boerries.,...&Wilson, Ian A..(2019).A small-molecule fusion inhibitor of influenza virus is orally active in mice.SCIENCE,363(6431),1056-+.
MLA	van Dongen, Maria J. P.,et al."A small-molecule fusion inhibitor of influenza virus is orally active in mice".SCIENCE 363.6431(2019):1056-+.