Peptides Derived from a Plant Protease Inhibitor of the Coagulation Contact System Decrease Arterial Thrombus Formation in a Murine Model, without Impairing Hemostatic Parameters.

Several plant protein inhibitors with anticoagulant properties have been studied and characterized, including the Delonix regia trypsin inhibitor (DrTI). This protein inhibits serine proteases (trypsin) and enzymes directly involved in coagulation, such as plasma kallikrein, factor XIIa, and factor XIa. In this study, we evaluated the effects of two new synthetic peptides derived from the primary sequence of DrTI in coagulation and thrombosis models to understand the mechanisms involved in the pathophysiology of thrombus formation as well as in the development of new antithrombotic therapies. Both peptides acted on in vitro hemostasis-related parameters, showing promising results, prolonging the Partially Activated Thromboplastin Time (aPTT) and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid. In murine models, for arterial thrombosis induced by photochemical injury, and platelet-endothelial interactions monitored by intravital microscopy, both peptides at doses of 0.5 mg/kg significantly extended the time of artery occlusion and modified the platelet adhesion and aggregation pattern with no changes in bleeding time, demonstrating the high biotechnological potential of both molecules.

Antibodies as Snakebite Antivenoms: Past and Future.

Snakebite envenomation is considered a neglected tropical disease, affecting tens of thousands of people each year. The recommended treatment is the use of antivenom, which is composed of immunoglobulins or immunoglobulin fragments obtained from the plasma of animals hyperimmunized with one (monospecific) or several (polyspecific) venoms. In this review, the efforts made in the improvement of the already available antivenoms and the development of new antivenoms, focusing on snakes of medical importance from sub-Saharan Africa and Latin America, are described. Some antivenoms currently used are composed of whole IgGs, whereas others use F(ab')2 fragments. The classic methods of attaining snake antivenoms are presented, in addition to new strategies to improve their effectiveness. Punctual changes in immunization protocols, in addition to the use of cross-reactivity between venoms from different snakes for the manufacture of more potent and widely used antivenoms, are presented. It is known that venoms are a complex mixture of components; however, advances in the field of antivenoms have shown that there are key toxins that, if effectively blocked, are capable of reversing the condition of in vivo envenomation. These studies provide an opportunity for the use of monoclonal antibodies in the development of new-generation antivenoms. Thus, monoclonal antibodies and their fragments are described as a possible alternative for the production of antivenoms, regardless of the venom. This review also highlights the challenges associated with their development.

Pathophysiology of COVID-19: Critical Role of Hemostasis.

The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths.