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@ARTICLE{Chatziefthymiou:602646,
author = {Chatziefthymiou, S. and Kuzikov, M. and Afandi, S. and
Crosas, E. and Pompidor, G. and Taberman, H. and
Windschügel, B. and Labahn, Joerg and Kolbe, M. and
Hakanpää, J.},
title = {{I}nhibitor screening and structural characterization of
virulence factors from {SARS}-{C}o{V}-2},
journal = {Acta crystallographica / Section A},
volume = {78},
number = {a2},
issn = {0108-7673},
address = {Oxford [u.a.]},
publisher = {Blackwell},
reportid = {PUBDB-2024-00707},
pages = {e333},
year = {2022},
abstract = {Coronavirus induced zoonotic diseases can cause pandemics
with unforeseeable consequences to human health and global
economy. Our project aims to screen and develop effective
therapeutics against SARS-CoV-2, targeting its
replication-transcription complex (RTC). Following an
interdisciplinary research approach, compound libraries of
approved drugs are used for the discovery of potent
inhibitors for proteins of the RTC and the binding mode of
these enzymeinhibitor complexes is studied by X-ray
crystallography. Our workflow includes the production of
proteins involved in the coronavirus RTC, the
high-throughput inhibitor screening with fluorescence-based
assays using drug repurposing libraries and the
structure/function analysis of the identified
enzyme-inhibitor complexes. The advantages of this approach
is that it is cost efficient, high-throughput, allows the
direct identification of potent inhibitors and ensures
optimal beamtime usage. Furthermore, such a platform can be
successfully used in future viral outbreaks. In this
presentation we will give an overview of this project and
the results achieved to date. We will focus on one of the
target proteins, namely the uridine-specific
endoribonuclease nsp15, and apart from the results from its
inhibitor screening we will also present findings that
allowed us to shed light on important activity determinants
of this enzyme.},
cin = {FS-PETRA-D / ITT / DOOR ; HAS-User / CSSB-HZI-MK},
ddc = {530},
cid = {I:(DE-H253)FS-PETRA-D-20210408 / I:(DE-H253)ITT-20160816 /
I:(DE-H253)HAS-User-20120731 /
I:(DE-H253)CSSB-HZI-MK-20210520},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633) / 6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-633 / G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P11-20150101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:001048207700273},
doi = {10.1107/S2053273322093986},
url = {https://bib-pubdb1.desy.de/record/602646},
}