Nogueira, Ruben Siedlarczyk;
Salu, Bruno Ramos;
Nardelli, Vinícius Goulart;
Bonturi, Camila Ramalho;
Pereira, Marina Rodrigues;
de Abreu Maffei, Francisco Humberto;
Cilli, Eduardo Maffud;
Oliva, Maria Luiza Vilela
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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Medientyp:
E-Artikel
Titel:
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
Beteiligte:
Nogueira, Ruben Siedlarczyk;
Salu, Bruno Ramos;
Nardelli, Vinícius Goulart;
Bonturi, Camila Ramalho;
Pereira, Marina Rodrigues;
de Abreu Maffei, Francisco Humberto;
Cilli, Eduardo Maffud;
Oliva, Maria Luiza Vilela
Erschienen:
Springer Science and Business Media LLC, 2023
Erschienen in:Thrombosis Journal
Sprache:
Englisch
DOI:
10.1186/s12959-022-00436-5
ISSN:
1477-9560
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>(p-BthTX-I)<jats:sub>2</jats:sub> 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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Objectives</jats:title>
<jats:p>To determine whether (p-BthTX-I)<jats:sub>2</jats:sub> K affects the hemostatic system.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>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)<jats:sub>2</jats:sub> 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<jats:sup>− 1</jats:sup> Rose Bengal in the carotid artery of male C57BL/6J mice using (p-BthTX-I)<jats:sub>2</jats:sub> K. Bleeding time was determined in mouse tails immersed in saline at 37 °C after (p-BthTX-I)<jats:sub>2</jats:sub> K (4.0 mg/kg and 8.0 mg/kg) or saline administration.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>(p-BthTX-I)<jats:sub>2</jats:sub> K prolonged the aPTT and PT by blocking kallikrein and FXa-like activities. Moreover, (p-BthTX-I)<jats:sub>2</jats:sub> K inhibited ADP-, collagen-, and arachidonic acid-induced platelet aggregation in a dose-dependent manner. Further, low concentrations of (p-BthTX-I)<jats:sub>2</jats:sub> K extended the time to artery occlusion by the formed thrombus. However, (p-BthTX-I)<jats:sub>2</jats:sub> K did not prolong the bleeding time in the mouse model of arterial thrombosis.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>These results demonstrate the antithrombotic activity of the peptide (p-BthTX-I)<jats:sub>2</jats:sub> K possibly by kallikrein inhibition, suggesting its strong biotechnological potential.</jats:p>
</jats:sec>