Therapeutic potential of snake venom: Toxin distribution and opportunities in deep learning for novel drug discovery

Bedraoui, Anas; Suntravat, Montamas; El Mejjad, Salim; Enezari, Salwa; Oukkache, Naoual; Sanchez, Elda E.; Galan, Jacob A.; El Fatimy, Rachid; Daouda, Tariq

doi:10.1016/j.medidd.2023.100175

Cited by 5 publications

(1 citation statement)

References 144 publications

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“…Snake venoms have long been studied for their complex biochemical properties and are primarily made up enzymatic and non-enzymatic proteins evolutionarily honed to alter any physiological pathway reachable by the bloodstream [11]. They represent an abundant source of bioactive molecules with a yet unrealised scope of potential medical applications in the leading areas of human death and disability, such as cardiovascular disease, diabetes, cancer, and chronic pain [12]. The coagulotoxic effects of snake venoms, while being critical for prey immobilisation and therefore predatory success and snakes' survival, are of particular significant interest in medical research for potential therapeutic applications, especially in the treatment of conditions related to thrombosis and cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

Coimbra,

Sanchez,

Lomonte

et al. 2024

Toxins

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This study investigated the intraspecific and interspecific variability in the venom effects of Agkistrodon viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrinogen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti, A. contortrix mokasen, A. contortrix phaeogaster, A. howardgloydi, A. piscivorus leucostoma, and A. piscivorus piscivorus. Notably, the phylogenetically disjunct lineages A. conanti, A. contortrix mokasen, and A. howardgloydi exhibited the most potent anticoagulant effects, indicating the independent amplification of a basal trait. Inhibition assays with the activated clotting enzymes Factors XIa, IXa, Xa, and IIa (thrombin) revealed that FXa inhibition is another basal trait amplified independently on multiple occasions within the genus, but with A. howardgloydi, notably more potent than all others. Phospholipid degradation and zymogen destruction were identified as mechanisms underlying the variability in venom effects observed experimentally and in previous clinical reports. Thromboelastography demonstrated that the venoms did not clot fibrinogen directly but affected fibrin clot strength by damaging fibrinogen and that thrombin was subsequently only able to cleave into weak, unstable clots. The ability to activate Protein C, an endogenous anticoagulant enzyme, varied across species, with some venoms exceeding that of A. contortrix contortrix, which previously yielded the protein diagnostic agent Protac®. Phylogenetic analysis suggested that both fibrinogen degradation and Protein C activation were each amplified multiple times within the genus, albeit with negative correlation between these two modes of action. This study highlights the evolutionary, clinical, and biodiscovery implications of venom variability in the Agkistrodon species, underscoring their dynamic evolution, emphasising the need for tailored clinical approaches, and highlighting the potential for novel diagnostic and therapeutic developments inspired by the unique properties of snake venoms.

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Section: Introductionmentioning

confidence: 99%

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

Coimbra,

Sanchez,

Lomonte

et al. 2024

Toxins

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An in-depth exploration of snake venom-derived molecules for drug discovery in advancing antiviral therapeutics

Hboub,

Ben Mrid,

Bouchmaa

et al. 2024

Heliyon

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Genetic variability in snake venom and its implications for antivenom development in sub-Saharan Africa

Ayesiga,

Okoro,

Taremba

et al. 2025

Transactions of the Royal Society of Tropical Medicine and Hygiene

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Snake venom, a complex mixture of proteins, has attracted human attention for centuries due to its associated mortality, morbidity and other therapeutic properties. In sub-Saharan Africa (SSA), where snakebites pose a significant health risk, understanding the genetic variability of snake venoms is crucial for developing effective antivenoms. The wide geographic distribution of venomous snake species in SSA countries demonstrates the need to develop specific and broad antivenoms. However, the development of broad antivenoms has been hindered by different factors, such as antivenom cross-reactivity and polygenic paratopes. While specific antivenoms have been hindered by the numerous snake species across the SSA region, current antivenoms, such as SAIMR polyvalent and Premium Serums & Vaccines, exhibit varying degrees of cross-reactivity. Such ability to cross-react enables the antivenoms to target multiple components from the different snake species. The advent of biotechnological innovations, including recombinant antibodies, small-molecule drugs, monoclonal antibodies and synthetic antivenoms, presents options for eliminating limitations associated with traditional plasma-derived antivenoms. However, challenges still persist, especially in SSA, in addressing genetic variability, as evidenced by inadequate testing capacity and limited genomic research facilities. This comprehensive review explores the genetic variability of snake venoms in SSA, emphasizing the venom composition of various snake species and their interactions. This information is critical in developing multiple strategies during antivenom development. Finally, it offers information concerning the need for extensive collaborative engagements, technological advancements and comprehensive genomic evaluations to produce targeted and effective antivenoms.

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Therapeutic potential of snake venom: Toxin distribution and opportunities in deep learning for novel drug discovery

Cited by 5 publications

References 144 publications

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

An in-depth exploration of snake venom-derived molecules for drug discovery in advancing antiviral therapeutics

Genetic variability in snake venom and its implications for antivenom development in sub-Saharan Africa

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