TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflammatory consequences
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:222 |
|---|---|
| Enthalten in: |
Antiviral research - 222(2024) vom: 22. Feb., Seite 105806 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Govednik, Tea [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 22.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.antiviral.2024.105806 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367022842 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367022842 | ||
| 003 | DE-627 | ||
| 005 | 20240229144052.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240114s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.antiviral.2024.105806 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1303.xml |
| 035 | |a (DE-627)NLM367022842 | ||
| 035 | |a (NLM)38211737 | ||
| 035 | |a (PII)S0166-3542(24)00014-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Govednik, Tea |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflammatory consequences |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2024 | ||
| 500 | |a Date Revised 22.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Anti-inflammatory activity | |
| 650 | 4 | |a Disulfides | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Spike | |
| 650 | 4 | |a Thiol-reacting compound | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a Vaccines |2 NLM | |
| 650 | 7 | |a Thioredoxins |2 NLM | |
| 650 | 7 | |a 52500-60-4 |2 NLM | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Disulfides |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 700 | 1 | |a Lainšček, Duško |e verfasserin |4 aut | |
| 700 | 1 | |a Kuhar, Urška |e verfasserin |4 aut | |
| 700 | 1 | |a Lachish, Marva |e verfasserin |4 aut | |
| 700 | 1 | |a Janežič, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Štrbenc, Malan |e verfasserin |4 aut | |
| 700 | 1 | |a Krapež, Uroš |e verfasserin |4 aut | |
| 700 | 1 | |a Jerala, Roman |e verfasserin |4 aut | |
| 700 | 1 | |a Atlas, Daphne |e verfasserin |4 aut | |
| 700 | 1 | |a Manček-Keber, Mateja |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Antiviral research |d 1983 |g 222(2024) vom: 22. Feb., Seite 105806 |w (DE-627)NLM012601756 |x 1872-9096 |7 nnns |
| 773 | 1 | 8 | |g volume:222 |g year:2024 |g day:22 |g month:02 |g pages:105806 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.antiviral.2024.105806 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 222 |j 2024 |b 22 |c 02 |h 105806 | ||