20.500.12556/DiRROS-18097-f3ed862f-7f85-7b25-18eb-c96d6b18fb22 TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequences 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. SARS-CoV-2 Disulfides Thiol-reacting compound Spike Anti-inflammatory activity true false true Elsevier Antiviral Research Angleški jezik Ni določen © 2024 The Authors. Published by Elsevier B.V. Neznano 2024-02-06 08:48:38 2024-02-06 09:20:55 2024-02-10 03:35:26 0000-00-00 00:00:00 2024 0 0 Št. članka: 105806; str. 1-13 [article no.] ǂ105806 Vol. 222 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2024-01-01 577:616 1872-9096 10.1016/j.antiviral.2024.105806 181304579 https://www.sciencedirect.com/science/article/pii/S0166354224000147?via%3Dihub 1 2632ad04-c4c4-11ee-8001-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=24587 RAZ_Govednik_Tea_2024.pdf RAZ_Govednik_Tea_2024.pdf 1 C082D1D70D9C5216904459B7957D861A 8dc267a30e88a0c5618ce5c1b56f3026be69fb8fb56cfe7fba7f95f5ce2b31cd 9273ed83-c4c8-11ee-8001-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=24591 Kemijski inštitut 0 0 0