Immune drug discovery from venoms

Jimenez, Rocio; Ikonomopoulou, Maria P.; Lopez, J. Alejandro; Miles, John J.

doi:10.1016/j.toxicon.2017.11.006

Cited by 14 publications

(6 citation statements)

References 103 publications

(92 reference statements)

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“…Colonic tissue samples from CTX-treated mice also showed a marked increase in regulatory CD4 + FoxP3 + T cells (T reg ), along with increased IL-10 and TGFβ concentrations, in the lamina propria [10]. These studies suggest that snake venom is a rich platform from which novel immunotherapies could be discovered [16].…”

Section: Introductionmentioning

confidence: 93%

Venom of the Red-Bellied Black Snake Pseudechis porphyriacus Shows Immunosuppressive Potential

Ryan

Lutzky

Herzig

et al. 2020

Toxins

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Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (Pseudechis porphyriacus) on human primary leukocytes using bead-based flow cytometry, mixed lymphocyte reaction, and cell viability assays. We show that venom treatment had a significant immunosuppressive effect, inhibiting the secretion of interleukin (IL)-2 and tumor necrosis factor (TNF) from purified human T cells by 90% or greater following stimulation with mitogen (phorbol 12-myristate 13-acetate and ionomycin) or via cluster of differentiation (CD) receptors, CD3/CD28. In contrast, venom treatment did not inhibit TNF or IL-6 release from antigen-presenting cells stimulated with lipopolysaccharide. The reduced cytokine release from T cells was not associated with inhibition of T cell proliferation or reduction of cell viability, consistent with an anti-inflammatory mechanism unrelated to the cell cycle. Deconvolution of the venom using reverse-phase HPLC identified four fractions responsible for the observed immunosuppressive activity. These data suggest that compounds from P. porphyriacus venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease.

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Section: Introductionmentioning

confidence: 93%

Venom of the Red-Bellied Black Snake Pseudechis porphyriacus Shows Immunosuppressive Potential

Ryan

Lutzky

Herzig

et al. 2020

Toxins

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“…Extensive research on the pharmacological properties is ongoing, and several of these venom-derived components are under clinical trials as potential therapeutic agents for several clinical indications. Currently, six FDA-approved venom-derived drugs are available on the market [ 110 ]. Pain is the most common presenting physical symptom and the primary reason for seeking medical care, which chronically affects people’s mental health and social life.…”

Section: Therapeutic Potential Of Bioactive Peptides and Proteins Fro...mentioning

confidence: 99%

Bioactive Peptides and Proteins from Centipede Venoms

et al. 2022

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Venoms are a complex cocktail of biologically active molecules, including peptides, proteins, polyamide, and enzymes widely produced by venomous organisms. Through long-term evolution, venomous animals have evolved highly specific and diversified peptides and proteins targeting key physiological elements, including the nervous, blood, and muscular systems. Centipedes are typical venomous arthropods that rely on their toxins primarily for predation and defense. Although centipede bites are frequently reported, the composition and effect of centipede venoms are far from known. With the development of molecular biology and structural biology, the research on centipede venoms, especially peptides and proteins, has been deepened. Therefore, we summarize partial progress on the exploration of the bioactive peptides and proteins in centipede venoms and their potential value in pharmacological research and new drug development.

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“…In addition, venom can interfere with the immune system regulating signaling pathways, tuning cytokine secretion or promoting cell migration. Understanding how they work can put toxins on the radar of new immunotherapies with venom or venom-derived products [61,62,81,82].…”

Section: Biotechnological Applications Of Pfpsmentioning

confidence: 99%

Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools

Rivera-de-Torre

Palacios-Ortega

Gavilanes

et al. 2019

Toxins

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Animal venoms are complex mixtures of highly specialized toxic molecules. Cnidarians and arachnids produce pore-forming proteins (PFPs) directed against the plasma membrane of their target cells. Among PFPs from cnidarians, actinoporins stand out for their small size and molecular simplicity. While native actinoporins require only sphingomyelin for membrane binding, engineered chimeras containing a recognition antibody-derived domain fused to an actinoporin isoform can nonetheless serve as highly specific immunotoxins. Examples of such constructs targeted against malignant cells have been already reported. However, PFPs from arachnid venoms are less well-studied from a structural and functional point of view. Spiders from the Latrodectus genus are professional insect hunters that, as part of their toxic arsenal, produce large PFPs known as latrotoxins. Interestingly, some latrotoxins have been identified as potent and highly-specific insecticides. Given the proteinaceous nature of these toxins, their promising future use as efficient bioinsecticides is discussed throughout this Perspective. Protein engineering and large-scale recombinant production are critical steps for the use of these PFPs as tools to control agriculturally important insect pests. In summary, both families of PFPs, from Cnidaria and Arachnida, appear to be molecules with promising biotechnological applications.

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Immune drug discovery from venoms

Cited by 14 publications

References 103 publications

Venom of the Red-Bellied Black Snake Pseudechis porphyriacus Shows Immunosuppressive Potential

Venom of the Red-Bellied Black Snake Pseudechis porphyriacus Shows Immunosuppressive Potential

Bioactive Peptides and Proteins from Centipede Venoms

Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools

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