2024-03-29T15:37:45Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/104162022-10-25T10:59:05Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
00925njm 22002777a 4500
dc
Rossey, Iebe
author
Gilman, Morgan S A
author
Kabeche, Stephanie C
author
Sedeyn, Koen
author
Wrapp, Daniel
author
Kanekiyo, Masaru
author
Chen, Man
author
Spitaels, Jan
author
Graham, Barney S
author
Schepens, Bert
author
McLellan, Jason S
author
Saelens, Xavier
author
Mas-Lloret, Vicente
author
Melero, Jose Antonio
author
2017
Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.
Nat Commun . 2017 Feb 13;8:14158.
http://hdl.handle.net/20.500.12105/10416
28194013
10.1038/ncomms14158
2041-1723
Nature communications
Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.