Functional characterization of a novel antithrombotic and thrombolytic metalloproteinase from Cerastes cerastes venom: a promising thromboprotective agent

Snake venom metalloproteinases (SVMPs) are abundant multidomain enzymes with diverse biological functions. This study aimed to purify and characterize a novel SVMP, CcVMP-III, from Cerastes cerastes venom and assess its protective effects in pulmonary embolism murine model. CcVMP-III (110 kDa) was purified by chromatographic techniques and partially sequenced using N-terminal and LC-MS/MS analyses. Biological activities were evaluated using coagulation parameters (aPTT, TT, PT), clot degradation, and fibrin plate lysis. Thromboprotective efficacy was assessed using a thrombin-induced pulmonary embolism model. CcVMP-III was identified as a class-III SVMP containing metalloproteinase, disintegrin-like, and cysteine-rich domains. It selectively prolonged aPTT and TT without affecting PT and exhibited strong fibrinolytic and thrombolytic activities. In vivo, it significantly prevented pulmonary thrombus formation, demonstrating marked thromboprotective efficacy. These findings emphasize the potential of CcVMP-III as a promising thromboprotective agent that may mitigate morbidity and mortality associated with thromboembolic events. This study describes the purification and characterization of CcVMP-III, a novel class-III metalloproteinase from Cerastes cerastes venom, exhibiting potent anticoagulant, fibrinolytic, and thrombolytic activities. CcVMP-III selectively prolonged the intrinsic and common coagulation pathways, promoted fibrin and clot degradation, and significantly reduced pulmonary thrombus formation in vivo, highlighting its potential as a thromboprotective agent in cardiovascular diseases.