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@ARTICLE{Lis:614237,
author = {Lis, Kinga and Plewka, Jacek and Menezes, Filipe and
Bielecka, Ewa and Chykunova, Yuliya and Pustelny, Katarzyna
and Niebling, Stephan and Garcia, Angelica Struve and
Garcia-Alai, Maria and Popowicz, Grzegorz M. and Czarna,
Anna and Kantyka, Tomasz and Pyrc, Krzysztof},
title = {{SARS}-{C}o{V}-2 {M}pro oligomerization as a potential
target for therapy},
journal = {International journal of biological macromolecules},
volume = {267},
issn = {0141-8130},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {PUBDB-2024-05777},
pages = {131392},
year = {2024},
abstract = {The main protease (Mpro) of SARS-CoV-2 is critical in the
virus's replication cycle, facilitating the maturation of
polyproteins into functional units. Due to its conservation
across taxa, Mpro is a promising target for broad-spectrum
antiviral drugs. Targeting Mpro with small molecule
inhibitors, such as nirmatrelvir combined with ritonavir
(Paxlovid™), which the FDA has approved for post-exposure
treatment and prophylaxis, can effectively interrupt the
replication process of the virus. A key aspect of Mpro's
function is its ability to form a functional dimer. However,
the mechanics of dimerization and its influence on
proteolytic activity remain less understood. In this study,
we utilized biochemical, structural, and molecular modelling
approaches to explore Mpro dimerization. We evaluated
critical residues, specifically Arg4 and Arg298, that are
essential for dimerization. Our results show that changes in
the oligomerization state of Mpro directly affect its
enzymatic activity and dimerization propensity. We
discovered a synergistic relationship influencing dimer
formation, involving both intra- and intermolecular
interactions. These findings highlight the potential for
developing allosteric inhibitors targeting Mpro, offering
promising new directions for therapeutic strategies.},
cin = {CSSB-CF-SPC},
ddc = {570},
cid = {I:(DE-H253)CSSB-CF-SPC-20210520},
pnm = {899 - ohne Topic (POF4-899) / CARE - Corona Accelerated
$R\&D$ in Europe (101005077)},
pid = {G:(DE-HGF)POF4-899 / G:(EU-Grant)101005077},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38582483},
UT = {WOS:001242446400001},
doi = {10.1016/j.ijbiomac.2024.131392},
url = {https://bib-pubdb1.desy.de/record/614237},
}