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TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequences
ID
Govednik, Tea
(
Avtor
),
ID
Lainšček, Duško
(
Avtor
),
ID
Kuhar, Urška
(
Avtor
),
ID
Lachish, Marva
(
Avtor
),
ID
Janežič, Sandra
(
Avtor
),
ID
Štrbenc, Malan
(
Avtor
),
ID
Krapež, Uroš
(
Avtor
),
ID
Jerala, Roman
(
Avtor
),
ID
Atlas, Daphne
(
Avtor
),
ID
Manček Keber, Mateja
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(7,11 MB)
MD5: EDD00EDF1D56B4035C0AF300435A8714
URL - Izvorni URL, za dostop obiščite
https://www.sciencedirect.com/science/article/pii/S0166354224000147?via%3Dihub
Galerija slik
Izvleček
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.
Jezik:
Angleški jezik
Ključne besede:
SARS-CoV-2
,
Disulfides
,
Thiol-reacting compound
,
Spike
,
Anti-inflammatory activity
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
VF - Veterinarska fakulteta
Datum objave:
01.01.2024
Leto izida:
2024
Št. strani:
13 str.
Številčenje:
Vol. 222, [article no.] ǂ105806
PID:
20.500.12556/RUL-153978
UDK:
577:616
ISSN pri članku:
1872-9096
DOI:
10.1016/j.antiviral.2024.105806
COBISS.SI-ID:
181304579
Datum objave v RUL:
17.01.2024
Število ogledov:
331
Število prenosov:
9
Metapodatki:
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Objavi na:
Gradivo je del revije
Naslov:
Antiviral research
Skrajšan naslov:
Antivir. res.
Založnik:
Elsevier Science
ISSN:
1872-9096
COBISS.SI-ID:
34758873
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
V4-2038
Naslov:
DNK cepiva in peptidnih inhibitorji proti SARS-CoV-2
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P4-0176
Naslov:
Sintezna biologija in imunologija
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P4-0053
Naslov:
Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Virofight project
Številka projekta:
H2020-FETOPEN-2018-2019-2020-01
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Yissum
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