Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms

Silva, Luciano C.; Pucca, Manuela Berto; Pessenda, Gabriela; Campos, Laa; Martinez, Edson Zangiacomi; Cerni, Felipe Augusto; Barbosa, José Elpídio

doi:10.1016/j.actatropica.2017.09.001

Cited by 21 publications

(24 citation statements)

References 47 publications

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“…Such studies have stimulated much research into the development of novel therapeutic approaches to tackle snakebite. These include the use of monoclonal antibody technologies to target key pathogenic toxins found in certain snake species (Laustsen et al, 2018;Silva et al, 2018), pathology rather than geographically-focused approaches to neutralizing venom toxins (Ainsworth et al, 2018), and the use of small molecule inhibitors designed to generically target specific toxin classes (Arias et al, 2017;Bryan-Quiros et al, 2019). The priority targets for these "next generation" snakebite therapeutics are the multifunctional toxins described herein (PLA2s, SVMP, SVSP, 3FTX) because of the major pathologies that they cause in snakebite victims.…”

Section: Therapeutic Implications Treating Snake Envenomationmentioning

confidence: 99%

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

et al. 2019

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Animal venoms have evolved over millions of years for prey capture and defense from predators and rivals. Snake venoms, in particular, have evolved a wide diversity of peptides and proteins that induce harmful inflammatory and neurotoxic effects including severe pain and paralysis, hemotoxic effects, such as hemorrhage and coagulopathy, and cytotoxic/myotoxic effects, such as inflammation and necrosis. If untreated, many envenomings result in death or severe morbidity in humans and, despite advances in management, snakebite remains a major public health problem, particularly in developing countries. Consequently, the World Health Organization recently recognized snakebite as a neglected tropical disease that affects ∼2.7 million p.a. The major protein classes found in snake venoms are phospholipases, metalloproteases, serine proteases, and three-finger peptides. The mechanisms of action and pharmacological properties of many snake venom toxins have been elucidated, revealing a complex multifunctional cocktail that can act synergistically to rapidly immobilize prey and deter predators. However, despite these advances many snake toxins remain to be structurally and pharmacologically characterized. In this review, the multifunctional features of the peptides and proteins found in snake venoms, as well as their evolutionary histories, are discussed with the view to identifying novel modes of action and improving snakebite treatments.

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Section: Therapeutic Implications Treating Snake Envenomationmentioning

confidence: 99%

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

et al. 2019

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“…In the field of human antibody fragments, Silva et al reported the use of phage display technology to select human scFvs against components from the venoms of Crotalus durissus terrificus and Bothrops jararacussu [53]. Based on an ELISA screening approach, three of these scFvs (B7, C11, and E9) were selected due to their cross-reactivity to components in both venoms.…”

Section: Oligonucleotides and Antibodiesmentioning

confidence: 99%

“…Haemolytic activity was fully inhibited by the combination of scFvs, while plasma-clotting was decreased but not fully prevented. Furthermore, the scFvs prolonged the survival of envenomed mice at ratios of 1:1 (w/w), but were maximally able to provide protection against lethality for 25% of the mice [53]. More research is thus needed to discover and engineer such human scFvs to gain improved efficacy.…”

Section: Oligonucleotides and Antibodiesmentioning

confidence: 99%

Recent Advances in Next Generation Snakebite Antivenoms

Knudsen¹,

Laustsen²

2018

Preprint

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With the inclusion of snakebite envenoming on the World Health Organisation’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Different technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins, as well as peptide and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors, varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.

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“…The field of human antibody fragments has for many years been championed by groups from Brazil and Mexico [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. In this field, Silva et al reported the use of phage display technology to select human scFvs against components from the venoms of Crotalus durissus terrificus and Bothrops jararacussu [ 71 ]. Based on an ELISA screening approach, three of these scFvs (B7, C11, and E9) were selected due to their cross-reactivity to components in both venoms.…”

Section: Oligonucleotides and Antibodiesmentioning

confidence: 99%

“…Haemolytic activity was fully inhibited by the combination of scFvs, while plasma-clotting was decreased but not fully prevented. Furthermore, the scFvs prolonged the survival of envenomed mice at ratios of 1:1 ( w / w ), but were maximally able to provide protection against lethality for 25% of the mice [ 71 ]. More research is thus needed to discover and engineer such human scFvs to gain improved efficacy.…”

Section: Oligonucleotides and Antibodiesmentioning

confidence: 99%

Recent Advances in Next Generation Snakebite Antivenoms

Knudsen

Laustsen

2018

TropicalMed

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With the inclusion of snakebite envenoming on the World Health Organization’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Various technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins as well as peptide- and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.

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Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms

Cited by 21 publications

References 47 publications

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

Recent Advances in Next Generation Snakebite Antivenoms

Recent Advances in Next Generation Snakebite Antivenoms

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