Abstract
Background:In Central and South America, snakebite envenomation is mainly caused by Bothrops spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. The available bothropic antivenoms are efficient in avoiding fatalities, but do not completely neutralize venom serine proteases, which are co-responsible for some disorders observed during envenomation.Methods:In order to search for tools to improve the antivenom’s, 6-mer peptides were designed based on a specific substrate for Bothrops jararaca venom serine proteases, and then synthesized, with the intention to selectively inhibit these enzymes.Results:Using batroxobin as a snake venom serine protease model, two structurally similar inhibitor peptides were identified. When tested on B. jararaca venom, one of the new inhibitors displayed a good potential to inhibit the activity of the venom serine proteases. These inhibitors do not affect human serine proteases as human factor Xa and thrombin, due to their selectivity.Conclusion:Our study identified two small peptides able to inhibit bothropic serine proteases, but not human ones, can be used as tools to enhance knowledge of the venom composition and function. Moreover, one promising peptide (pepC) was identified that can be explored in the search for improving Bothrops spp. envenomation treatment.
Highlights
In Central and South America, snakebite envenomation is mainly caused by Bothrops spp. snakes, whose venoms feature significant biochemical richness, including serine proteases
The goal of this work is the identification of Bothrops snake venom serine protease (SVSP) inhibitory peptides, inert to human serine protease (hSP), which can be used as tools for increasing bothropic SVSPs knowledge and, in perspective, in combination to antivenom for treatment improvement and enhancement of the envenomed patient’s clinical picture
Considering recent studies reporting residual SVSPs activity after bothropic antivenom treatment [9, 10, 13], we decided to search for peptides able to inhibit these proteins, which are enzymes co-responsible for hemostatic disorders observed on snakebites envenomation
Summary
In Central and South America, snakebite envenomation is mainly caused by Bothrops spp. snakes, whose venoms feature significant biochemical richness, including serine proteases. Most snakebite envenomation cases in Central and South America are caused by snakes from the Bothrops genus. Typical clinical symptoms of envenomation caused by Bothrops spp. snakebites include pain, blisters and hemostatic disturbances, and in more severe cases, abscesses, necrosis, and acute kidney failure [2]. These manifestations are mainly associated with the action of metalloproteases (SVMPs) and serine proteases (SVSPs) [3]. Some SVSPs display fibrinogenolytic activity and are classified as thrombin-like enzymes (TLEs) [8]. TLEs usually do not cleave both chains of fibrinogen, neither activate other coagulation factors such as factor XIII, causing an imbalance in the victim’s hemostatic system [8]
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