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TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequences
ID
Govednik, Tea
(
Author
),
ID
Lainšček, Duško
(
Author
),
ID
Kuhar, Urška
(
Author
),
ID
Lachish, Marva
(
Author
),
ID
Janežič, Sandra
(
Author
),
ID
Štrbenc, Malan
(
Author
),
ID
Krapež, Uroš
(
Author
),
ID
Jerala, Roman
(
Author
),
ID
Atlas, Daphne
(
Author
),
ID
Manček Keber, Mateja
(
Author
)
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https://www.sciencedirect.com/science/article/pii/S0166354224000147
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Abstract
After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.
Language:
English
Keywords:
SARS-CoV-2
,
disulfides
,
thiol-reacting compound
,
spike
,
anti-inflammatory activity
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
VF - Veterinary Faculty
Publication status:
Published
Publication version:
Version of Record
Year:
2024
Number of pages:
13 str.
Numbering:
Vol. 222, art. 105806
PID:
20.500.12556/RUL-153978
UDC:
577:616
ISSN on article:
1872-9096
DOI:
10.1016/j.antiviral.2024.105806
COBISS.SI-ID:
181304579
Publication date in RUL:
17.01.2024
Views:
734
Downloads:
70
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Record is a part of a journal
Title:
Antiviral research
Shortened title:
Antivir. res.
Publisher:
Elsevier
ISSN:
1872-9096
COBISS.SI-ID:
34758873
Licences
License:
CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
Link:
http://creativecommons.org/licenses/by-nc/4.0/
Description:
A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.
Projects
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
V4-2038
Name:
DNK cepiva in peptidni inhibitorji proti SARS-CoV-2
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P4-0176
Name:
Sintezna biologija in imunologija
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P4-0092
Name:
Zdravje živali, okolje in varna hrana
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P4-0053
Name:
Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih
Funder:
EC - European Commission
Funding programme:
H2020
Project number:
899619
Name:
General-purpose virus-neutralizing engulfing shells with modular target-specificity
Acronym:
VIROFIGHT
Funder:
Other - Other funder or multiple funders
Funding programme:
The Hebrew University, Yissum
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