The chemistry of snake venom and its medicinal potential

Nature Reviews Chemistry, Journal Year: 2022, Volume and Issue: 6(7), P. 451 - 469

Published: June 10, 2022

Language: Английский

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ToxinPred2: an improved method for predicting toxicity of proteins

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 23(5)

Published: April 20, 2022

Proteins/peptides have shown to be promising therapeutic agents for a variety of diseases. However, toxicity is one the obstacles in protein/peptide-based therapy. The current study describes web-based tool, ToxinPred2, developed predicting proteins. This an update ToxinPred mainly peptides and small method has been trained, tested evaluated on three datasets curated from recent release SwissProt. To provide unbiased evaluation, we performed internal validation 80% data external remaining 20% data. We implemented following techniques protein toxicity; (i) Basic Local Alignment Search Tool-based similarity, (ii) Motif-EmeRging with Classes-Identification-based motif search (iii) Prediction models. Similarity motif-based achieved high probability correct prediction poor sensitivity/coverage, whereas models based machine-learning balance sensitivity specificity reasonably accuracy. Finally, hybrid that combined all approaches maximum area under receiver operating characteristic curve around 0.99 Matthews correlation coefficient 0.91 dataset. In addition, alternate realistic datasets. best machine learning web server named 'ToxinPred2', which available at https://webs.iiitd.edu.in/raghava/toxinpred2/ standalone version https://github.com/raghavagps/toxinpred2. general proteins regardless their source origin.

Language: Английский

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Snake Envenomation

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 386(1), P. 68 - 78

Published: Jan. 5, 2022

Snake envenomation is a global health problem. The range of clinical sequelae includes thromboses and neuromuscular paralysis. Antivenoms made in horses sheep are the treatments choice but require accurate identification bite source can cause anaphylaxis serum sickness.

Language: Английский

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Modern venomics—Current insights, novel methods, and future perspectives in biological and applied animal venom research

GigaScience, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 1, 2022

Abstract Venoms have evolved >100 times in all major animal groups, and their components, known as toxins, been fine-tuned over millions of years into highly effective biochemical weapons. There are many outstanding questions on the evolution toxin arsenals, such how venom genes originate, contributes to fitness venomous species, which modifications at genomic, transcriptomic, protein level drive evolution. These received particularly little attention outside snakes, cone snails, spiders, scorpions. Venom compounds further become a source inspiration for translational research using diverse bioactivities various applications. We highlight here recent advances new strategies modern venomics discuss technological innovations multi-omic methods dramatically improve animals. The study genomes through CRISPR knockdown technologies will increase our understanding toxins evolve functions they different ontogenetic stages during development Mass spectrometry imaging combined with spatial transcriptomics, situ hybridization techniques, computer tomography gives us insights distribution system function apparatus. All these evolutionary biological contribute more efficiently identify compounds, can then be synthesized or produced adapted expression systems test bioactivity. Finally, we critically agrochemical, pharmaceutical, therapeutic, diagnostic (so-called translational) aspects venoms from humans benefit.

Language: Английский

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Clinical aspects of snakebite envenoming and its treatment in low-resource settings

The Lancet, Journal Year: 2023, Volume and Issue: 401(10385), P. 1382 - 1398

Published: March 14, 2023

Language: Английский

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Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 22, 2024

Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. Where mainly caused by venom toxins that induce cardiovascular disturbances, neurotoxicity, acute kidney injury, morbidity directly or indirectly destroy cells degrade the extracellular matrix. These are referred to as 'tissue-damaging toxins' have previously been classified in various ways, most of which based on tissues being affected (e.g., cardiotoxins, myotoxins). This categorisation, however, primarily phenomenological not mechanistic. In this review, we propose alternative way classifying cytotoxins their mechanistic effects rather than using a description organ- tissue-based. The mechanisms toxin-induced tissue damage clinical implications discussed. review contributes our understanding fundamental biological processes associated with snakebite envenoming, may pave knowledge-based search novel therapeutic options.

Language: Английский

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Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(735)

Published: Feb. 21, 2024

Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents considerable challenge to the development of universal antivenom. Here, we used synthetic human antibody library find and develop an that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our bound diverse toxin variants with high affinity, blocked binding nicotinic acetylcholine receptor vitro, protected mice lethal challenge. Structural analysis antibody-toxin complex revealed mode mimics receptor-toxin interaction. overall workflow presented generalizable antibodies target conserved epitopes among antigenically targets, it offers promising framework creation monoclonal antibody–based antivenom treat snakebite envenoming.

Language: Английский

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

Transactions of the Royal Society of Tropical Medicine and Hygiene, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract 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 significant health risk, understanding the genetic variability snake venoms is crucial developing effective antivenoms. The wide geographic distribution venomous species in SSA countries demonstrates need develop specific broad However, development antivenoms been hindered by different factors, such as antivenom cross-reactivity polygenic paratopes. While have numerous across region, current antivenoms, SAIMR polyvalent Premium Serums & Vaccines, exhibit varying degrees cross-reactivity. Such ability cross-react enables target multiple components from species. advent biotechnological innovations, including recombinant antibodies, small-molecule drugs, monoclonal antibodies synthetic presents options eliminating limitations with traditional plasma-derived challenges still persist, especially SSA, addressing variability, evidenced inadequate testing capacity limited genomic research facilities. This comprehensive review explores emphasizing venom composition various their interactions. information critical strategies during development. Finally, it offers concerning extensive collaborative engagements, technological advancements evaluations produce targeted

Language: Английский

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Biogeographical venom variation in the Indian spectacled cobra (Naja naja) underscores the pressing need for pan-India efficacious snakebite therapy

PLoS neglected tropical diseases, Journal Year: 2021, Volume and Issue: 15(2), P. e0009150 - e0009150

Published: Feb. 18, 2021

Background Snake venom composition is dictated by various ecological and environmental factors, can exhibit dramatic variation across geographically disparate populations of the same species. This molecular diversity undermine efficacy snakebite treatments, as antivenoms produced against from one population may fail to neutralise others. India world’s hotspot, with 58,000 fatalities 140,000 morbidities occurring annually. Spectacled cobra ( Naja naja ) Russell’s viper Daboia russelii are known cause majority these envenomations, in part due their near country-wide distributions. However, impact differing ecologies environment on compositions has not been comprehensively studied. Methods Here, we used a multi-disciplinary approach consisting proteomics, biochemical pharmacological analyses, vivo research comparatively analyse N . venoms broad region (>6000 km; seven populations) covering India’s six distinct biogeographical zones. Findings By generating most comprehensive pan-Indian proteomic toxicity profiles date, unveil considerable differences composition, effects potencies geographically-distinct this species and, through use immunological assays preclinical experiments, demonstrate alarming repercussions antivenom therapy. We find that commercially-available fails effectively envenomations , including complete lack neutralisation desert population. Conclusion Our findings highlight significant influence ecology snake potency, stress pressing need innovate pan-India effective safeguard lives, limbs livelihoods country’s 200,000 annual victims.

Language: Английский

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The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming

Toxins, Journal Year: 2021, Volume and Issue: 13(7), P. 451 - 451

Published: June 29, 2021

A global strategy, under the coordination of World Health Organization, is being unfolded to reduce impact snakebite envenoming. One pillars this strategy ensure safe and effective treatments. The mainstay in therapy envenoming administration animal-derived antivenoms. In addition, new therapeutic options are explored, including recombinant antibodies natural synthetic toxin inhibitors. review, snake venom toxins classified terms their abundance toxicity, priority actions proposed search for metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger (3FTx), serine proteinase (SVSP) Natural inhibitors include compounds isolated from plants, animal sera, mast cells, whereas comprise a wide range molecules variable chemical nature. Some most promising inhibitors, especially SVMP PLA2 have been developed other diseases repurposed drugs aimed at controlling endogenous processes generated course pursued. present review summarizes some developments field discusses issues that need be considered translation knowledge improve therapies tackling

Language: Английский

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