Protease Activity Profiling of Snake Venoms Using High-Throughput Peptide Screening

Abstract

Snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) are among the most abundant enzymes in many snake venoms, particularly among viperids. These proteinases are responsible for some of the clinical manifestations classically seen in viperid envenomings, including hemorrhage, necrosis, and coagulopathies. The objective of this study was to investigate the enzymatic activities of these proteins using a high-throughput peptide library to screen for the proteinase targets of the venoms of five viperid (Echis carinatus, Bothrops asper, Daboia russelii, Bitis arietans, Bitis gabonica) and one elapid (Naja nigricollis) species of high medical importance. The proteinase activities of these venoms were each tested against 360 peptide substrates, yielding 2160 activity profiles. A nonlinear regression model that accurately described the observed enzymatic activities was fitted to the experimental data, allowing for the comparison of cleavage rates across species. In this study, previously unknown protein targets of snake venom proteinases were identified, potentially implicating novel human and animal proteins that may be involved in the pathophysiology of viper envenomings. The functional relevance of these targets was further evaluated and discussed. These new findings may contribute to our understanding of the clinical manifestations and underlying biochemical mechanisms of snakebite envenoming by viperid species.

Biogeographical venom variation in the Indian spectacled cobra (Naja naja) underscores the pressing need for pan-India efficacious snakebite therapy

“…SVMPs in Elapidae snakes have been shown to affect haemostasis by inhibiting the aggregation of platelets [ 54 ]. Similarly, SVSPs too could interfere with the clotting cascade by exhibiting thrombin- and plasminogen-like activities [ 55 – 57 ]. In addition to fibrinogenolysis, kallikrein-like SVSPs are also known to affect the blood pressure by inducing the release of hypotensive bradykinin [ 58 ].…”

Severe Acute Thromboinflammation: Case Report of Individualized Homeopathic Treatment

“…Interestingly, snake venoms contain serine proteases with direct fibrinolytic action, as well as metalloproteinases with both pro-and anti-coagulating effects, whence their complex influence on the coagulation cascade. 30 There are several case reports in the literature of disseminated intravascular coagulation after multiple honeybee stings, and also after bee venom acupuncture. [31][32][33] The state of hypercoagulability, therefore, corroborated the remedy selection, which the patient kept taking every 2 hours during the first 4 days, until the hypercoagulability state improved dramatically, fever had stopped, urticaria had almost disappeared, the inflammation marker CRP had halved, and the results of three PCR tests for SARS-CoV-2 were reported negative.…”

The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming

“…SVMPs act on an ample spectrum of substrates, as revealed by proteomic and otheranalyses [ 50 , 51 ]. In terms of their pathophysiological effects, their actions on extracellular matrix components and on coagulation factors determine their ability to induce local and systemic hemorrhage, and coagulopathies, respectively [ 52 ].…”