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@ARTICLE{Vollmer:637726,
author = {Vollmer, Benjamin and Ebel, Henriette and Rees, Renate and
Nentwig, Julia and Mulvaney, Thomas and Schünemann, Jürgen
and Krull, Jens and Topf, Maya and Görlich, Dirk and
Gruenewald, Kay},
title = {{A} nanobody specific to prefusion glycoprotein {B}
neutralizes {HSV}-1 and {HSV}-2},
journal = {Nature},
volume = {646},
number = {8084},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {PUBDB-2025-03899},
pages = {433 - 441},
year = {2025},
abstract = {The nine human herpesviruses, including herpes simplex
virus 1 and 2, human cytomegalovirus and Epstein–Barr
virus, present a significant burden to global public
health1. Their envelopes contain at least ten different
glycoproteins, which are necessary for host cell tropism,
attachment and entry2. The best conserved among them,
glycoprotein B (gB), is essential as it performs membrane
fusion by undergoing extensive rearrangements from a
prefusion to postfusion conformation. At present, there are
no antiviral drugs targeting gB or neutralizing antibodies
directed against its prefusion form, because of the
difficulty in structurally determining and using this
metastable conformation. Here we show the isolation of
prefusion-specific nanobodies, one of which exhibits strong
neutralizing and cross-species activity. By mutational
stabilization we solved the herpes simplex virus 1 gB
full-length prefusion structure, which allowed the bound
epitope to be determined. Our analyses show the
membrane-embedded regions of gB and previously unresolved
structural features3,4, including a new fusion loop
arrangement, providing insights into the initial
conformational changes required for membrane fusion. Binding
an epitope spanning three domains, proximal only in the
prefusion state, the nanobody keeps wild-type HSV-2 gB in
this conformation and enabled its native prefusion structure
to be determined. This also indicates the mode of
neutralization and an attractive avenue for antiviral
interventions.},
cin = {CSSB-LIV-KG / CSSB-LIV/UKE-MT},
ddc = {500},
cid = {I:(DE-H253)CSSB-LIV-KG-20220525 /
$I:(DE-H253)CSSB-LIV_UKE-MT-20220525$},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633)},
pid = {G:(DE-HGF)POF4-633},
experiment = {EXP:(DE-H253)ALFM-20250101 / EXP:(DE-H253)cryo-EM-20250101
/ EXP:(DE-H253)SPC-20250101},
typ = {PUB:(DE-HGF)16},
doi = {10.1038/s41586-025-09438-5},
url = {https://bib-pubdb1.desy.de/record/637726},
}