Phage display as a novel promising antivenom therapy: A review

Roncolato, Eduardo Crosara; Campos, Laa; Pessenda, Gabriela; Silva, Luciano Costa e; Furtado, Gilvan Pessoa; Barbosa, José Elpídio

doi:10.1016/j.toxicon.2014.11.001

Cited by 42 publications

(23 citation statements)

References 47 publications

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“…Animal-derived antivenoms are considered the only specific therapy available for treating snakebite envenoming (Maduwage and Isbister, 2014;Slagboom et al, 2017;Ainsworth et al, 2018). These consist of polyclonal immunoglobulins, such as intact IgGs or F(ab') 2 , or Fab fragments (Ouyang et al, 1990;Maduwage and Isbister, 2014;Roncolato et al, 2015), derived from hyperimmune animal serum/plasma (typically horse or sheep). When used rapidly and appropriately, they are capable of neutralizing life-threatening systemic envenoming, for example pathologies such as venom-induced coagulopathy, hemorrhage, neurotoxic effects, and/or hypotensive shock (Warrell, 1992;Calvete et al, 2009;Maduwage and Isbister, 2014;Slagboom et al, 2017;Ainsworth et al, 2018).…”

Section: Therapeutic Implications Treating Snake Envenomationmentioning

confidence: 99%

“…Polyvalent antivenoms are therefore designed to address the limited paraspecific cross-reactivity of monovalent antivenoms by stimulating the production of antibodies against diverse venom toxins found in different snake species, and to avoid issues relating to the wrong antivenom being given due to a lack of existing snakebite diagnostic tools (O'leary and Isbister, 2009;Abubakar et al, 2010). However, polyvalent therapies come with disadvantages-larger therapeutic dose are required to effect cure, potentially resulting in an increased risk of adverse reactions, and in turn increasing cost to impoverished snakebite victims (Hoogenboom, 2005;O'leary and Isbister, 2009;Deshpande et al, 2013;Roncolato et al, 2015).…”

Section: Therapeutic Implications Treating Snake Envenomationmentioning

confidence: 99%

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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%

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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“…The phenomenon is still poorly investigated and understood due to its inherent complexity. The importance of being able to determine the presence of synergism and having a mechanistic model for how venoms exert their toxic effects is, however, becoming increasingly more important driven by a trend in antivenom development where biotechnological approaches are being employed to identify specific antitoxins targeting individual toxins of medical importance (Roncolato et al, 2015, Richard et al, 2013, Chavanayarn et al, 2012, Laustsen et al, 2016A, Laustsen et al, 2016B, Carmo et al, 2015. Therefore, when selecting which toxin targets to focus on, it is important to focus both on toxins that are medically relevant on an individual basis (Laustsen et al, 2015C) and on potential non-toxic venom components, which may enhance the effect of other components through synergism .…”

Section: Resultsmentioning

confidence: 99%

Toxin synergism in snake venoms

Laustsen

2016

Toxin Reviews

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Synergism between venom toxins exists for a range of snake species. Synergism can be derived from both intermolecular interactions and supramolecular interactions between venom components and can be the result of toxins targeting the same protein, biochemical pathway, or physiological process. Few simple systematic tools and methods for determining the presence of synergism exist, but include co-administration of venom components and assessment of Accumulated Toxicity Scores. A better understanding of how to investigate synergism in snake venoms may help unravel strategies for developing novel therapies against snakebite envenoming by elucidating mechanisms for toxicity and interactions between venom components.

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“…Therefore, decreasing the load of C. jejuni in poultry products decreases the risk of people getting sick, and in that sense phage therapy may also be considered to have an indirect “probiotic” activity. On a note side, research on the use of phages in other applications, such as construction of antivenoms (phage display), and biocontrol in food manufacturing is still ongoing, yet looks very promising [18, 26, 34]. …”

Section: Phage Therapy Nowmentioning

confidence: 99%

Phage Therapy in Bacterial Infections Treatment: One Hundred Years After the Discovery of Bacteriophages

et al. 2016

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The therapeutic use of bacteriophages has seen a renewal of interest blossom in the last few years. This reversion is due to increased difficulties in the treatment of antibiotic-resistant strains of bacteria. Bacterial resistance to antibiotics, a serious problem in contemporary medicine, does not implicate resistance to phage lysis mechanisms. Lytic bacteriophages are able to kill antibiotic-resistant bacteria at the end of the phage infection cycle. Thus, the development of phage therapy is potentially a way to improve the treatment of bacterial infections. However, there are antibacterial phage therapy difficulties specified by broadening the knowledge of the phage nature and influence on the host. It has been shown during experiments that both innate and adaptive immunity are involved in the clearance of phages from the body. Immunological reactions against phages are related to the route of administration and may vary depending on the type of bacterial viruses. For that reason, it is very important to test the immunological response of every single phage, particularly if intravenous therapy is being considered. The lack of these data in previous years was one of the reasons for phage therapy abandonment despite its century-long study. Promising results of recent research led us to look forward to a phage therapy that can be applied on a larger scale and subsequently put it into practice.

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Phage display as a novel promising antivenom therapy: A review

Cited by 42 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

Toxin synergism in snake venoms

Phage Therapy in Bacterial Infections Treatment: One Hundred Years After the Discovery of Bacteriophages

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