| Title: | TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequences |
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| Authors: | 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), et al. |
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| Files: |  URL - Source URL, visit https://www.sciencedirect.com/science/article/pii/S0166354224000147?via%3Dihub
 PDF - Presentation file, download (7,11 MB)
MD5: C082D1D70D9C5216904459B7957D861A
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  KI - National Institute of Chemistry
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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. |
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| Keywords: | SARS-CoV-2, Disulfides, Thiol-reacting compound, Spike, Anti-inflammatory activity |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 01.01.2024 |
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| Publisher: | Elsevier |
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| Year of publishing: | 2024 |
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| Number of pages: | str. 1-13 |
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| Numbering: | Vol. 222, [article no.] ǂ105806 |
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| Source: | Antiviral Research |
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| PID: | 20.500.12556/DiRROS-18097-f3ed862f-7f85-7b25-18eb-c96d6b18fb22  |
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| UDC: | 577:616 |
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| ISSN on article: | 1872-9096 |
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| DOI: | 10.1016/j.antiviral.2024.105806 |
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| COBISS.SI-ID: | 181304579 |
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| Copyright: | © 2024 The Authors. Published by Elsevier B.V. |
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| Note: | Št. članka: 105806;
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| Publication date in DiRROS: | 06.02.2024 |
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| Views: | 326 |
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| Downloads: | 136 |
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