A snake venom-analog peptide that inhibits SARS-CoV-2 and papain-like protease displays antithrombotic activity in mice arterial thrombosis model, without interfering with bleeding time

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Federal de São Paulo (UNIFESP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorNogueira, Ruben Siedlarczyk-
Autor(es): dc.creatorSalu, Bruno Ramos-
Autor(es): dc.creatorNardelli, Vinícius Goulart-
Autor(es): dc.creatorBonturi, Camila Ramalho-
Autor(es): dc.creatorPereira, Marina Rodrigues-
Autor(es): dc.creatorde Abreu Maffei, Francisco Humberto-
Autor(es): dc.creatorCilli, Eduardo Maffud-
Autor(es): dc.creatorOliva, Maria Luiza Vilela-
Data de aceite: dc.date.accessioned2025-08-21T21:13:33Z-
Data de disponibilização: dc.date.available2025-08-21T21:13:33Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1186/s12959-022-00436-5-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/248120-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/248120-
Descrição: dc.descriptionBackground: (p-BthTX-I)2 K, a dimeric analog peptide derived from the C-terminal region of phospholipase A2-like bothropstoxin-I (p-BthTX-I), is resistant to plasma proteolysis and inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains with weak cytotoxic effects. Complications of SARS-CoV-2 infection include vascular problems and increased risk of thrombosis; therefore, studies to identify new drugs for treating SARS-CoV-2 infections that also inhibit thrombosis and minimize the risk of bleeding are required. Objectives: To determine whether (p-BthTX-I)2 K affects the hemostatic system. Methods: Platelet aggregation was induced by collagen, arachidonic acid, and adenosine diphosphate (ADP) in the Chronolog Lumi-aggregometer. The coagulation activity was evaluated by determining activated partial thromboplastin clotting time (aPTT) and prothrombin time (PT) with (p-BthTX-I)2 K (5.0–434.5 µg) or 0.9% NaCl. Arterial thrombosis was induced with a 540 nm laser and 3.5–20 mg kg− 1 Rose Bengal in the carotid artery of male C57BL/6J mice using (p-BthTX-I)2 K. Bleeding time was determined in mouse tails immersed in saline at 37 °C after (p-BthTX-I)2 K (4.0 mg/kg and 8.0 mg/kg) or saline administration. Results: (p-BthTX-I)2 K prolonged the aPTT and PT by blocking kallikrein and FXa-like activities. Moreover, (p-BthTX-I)2 K inhibited ADP-, collagen-, and arachidonic acid-induced platelet aggregation in a dose-dependent manner. Further, low concentrations of (p-BthTX-I)2 K extended the time to artery occlusion by the formed thrombus. However, (p-BthTX-I)2 K did not prolong the bleeding time in the mouse model of arterial thrombosis. Conclusion: These results demonstrate the antithrombotic activity of the peptide (p-BthTX-I)2 K possibly by kallikrein inhibition, suggesting its strong biotechnological potential.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionDepartment of Biochemistry Universidade Federal de São Paulo (UNIFESP), SP-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Institute of Chemistry Universidade Estadual Paulista (UNESP), SP-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Universidade Estadual Paulista (UNESP), SP-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Institute of Chemistry Universidade Estadual Paulista (UNESP), SP-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Universidade Estadual Paulista (UNESP), SP-
Descrição: dc.descriptionFAPESP: 2017/06630-7-
Descrição: dc.descriptionFAPESP: 2019/22243-9-
Descrição: dc.descriptionFAPESP: 2020/01512-9-
Descrição: dc.descriptionFAPESP: 2020/05761-3-
Idioma: dc.languageen-
Relação: dc.relationThrombosis Journal-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectBleeding-
Palavras-chave: dc.subjectCOVID-19-
Palavras-chave: dc.subjectCysteine-protease-
Palavras-chave: dc.subjectPapain-like protease-
Palavras-chave: dc.subjectPlatelets-
Palavras-chave: dc.subjectSARS-CoV-2-
Palavras-chave: dc.subjectThrombosis-
Título: dc.titleA snake venom-analog peptide that inhibits SARS-CoV-2 and papain-like protease displays antithrombotic activity in mice arterial thrombosis model, without interfering with bleeding time-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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