The Venom Revolution in Biomedicine: Unlocking Nature’s Toxin Toolkit for Therapeutic Innovation

Abstract

Once known only for its deadly effects, venom is now valued for its medicinal potential. The transformation of venomous substances into therapeutic agents, focusing on the synergy between natural toxins and drugs, is a recent topic of interest to the scientific community worldwide. Venom is a concoction of various biomolecules, including proteins, enzymes, peptides, protease inhibitors, and more. This review focuses on different categories of venomous species, their venom composition, the mechanism of venom deployment, and the pharmacokinetics. Besides this, it also focuses on the technological innovations while tracing venom's medical use from ancient practices to modern therapies. Additionally, it addresses the challenges and future directions, such as regulatory obstacles related to the approval processes for venom-derived drugs, illustrating the ongoing evolution from toxins to cure.

Graphical Abstract

Highlights

• •Discusses the transformation of venoms into therapeutic agents.
• •Highlights key venom-based drugs and their potential in treating diseases.
• •Reviews challenges and evolution in venom drug discovery.
• •Provides perspective on the future of venom-derived pharmaceuticals.

1. Introduction

The historical pursuit of transforming ordinary substances into valuable resources has found a modern scientific counterpart in venom research. For centuries, venomous snakes, scorpions, spiders, and marine creatures were primarily feared for their lethal effects. However, contemporary research has revealed that these complex natural toxins harbour an array of bioactive compounds with immense therapeutic potential. Venoms are composed of diverse proteins, peptides, small molecules, and neurotransmitters that target specific physiological pathways with remarkable precision, making them powerful candidates for drug discovery and molecular research [1].

The unique pharmacological properties of venom-derived drugs, such as Ziconotide from cone snail venom for severe pain management and Captopril from the Brazilian pit viper for hypertension treatment, have led to their regulatory approval for conditions like chronic pain, cancer, hypertension, and thrombosis, highlighting the immense potential of venoms as a reservoir of bioactive molecules for therapeutic applications [1]. Given that a single venom can contain hundreds of distinct compounds and that many venomous species remain unexplored, the field holds vast opportunities for further medical breakthroughs.

Beyond their medical applications, venoms offer a fascinating window into evolutionary biology. Venom systems have evolved independently over 100 times across at least eight different phyla, showcasing an extraordinary example of convergent evolution. The molecular diversity within venoms arises from dynamic evolutionary pressures that shape their composition to optimize prey immobilization, digestion, or defence mechanisms [2]. This evolutionary adaptability further underscores venoms’ unique biochemical richness and their untapped potential for biotechnological applications.

Despite these promising prospects, venom research is fraught with challenges. The complexity of venom composition makes the identification and isolation of pharmacologically relevant compounds a formidable task. Additionally, translating venom-derived compounds into clinically viable drugs requires rigorous pharmacological and toxicological evaluations. The lack of ecological context in pharmacological studies further complicates the understanding of venom function beyond its medical implications. Regulatory hurdles also pose significant barriers, as the development and approval of venom-derived therapeutics demand extensive preclinical and clinical validation. Moreover, ethical concerns regarding venom extraction from live animals and sustainability must be addressed to ensure responsible and humane scientific progress.

This review explores the vast biological diversity of venom-derived proteins, enzymes, peptides, and protease inhibitors, their molecular mechanisms of action, and their efficacy and safety profiles in preclinical and clinical studies. It also discusses emerging therapeutic strategies, recent technological advancements, and regulatory challenges, providing a comprehensive overview of the transformation of venoms from feared natural toxins to invaluable medical resources. By bridging the gap between venom ecology, pharmacology, and biotechnology, this review underscores the immense promise of venom-based therapeutics in modern medicine.

2. Venom biology: species diversity, toxin profiles, and mechanisms of action

Venomous species, spanning vertebrates (fish, amphibians, reptiles, birds, mammals) and invertebrates (coelenterates, worms, arthropods, molluscs, echinoderms) produce potent toxins capable of causing harm or death in small quantities. Venom deployment relies on specialised structures such as fangs, stingers, nematocysts, venom glands, and cnidocysts for efficient toxin delivery [3]. These venoms primarily target the nervous and cardiovascular systems, inducing paralysis, cardiovascular collapse, or tissue necrosis. While some organisms inject venom rapidly, others release it in controlled doses, reflecting finely evolved strategies suited to their ecological roles. Fig. 1 illustrates key venomous taxa and their associated glands and tissues. Across snakes, spiders, scorpions, cone snails, sea slugs, and venomous frogs, toxin delivery mechanisms reveal remarkable adaptations for predation and defence. Understanding these systems provides insights into species biology, venom pharmacokinetics, and the therapeutic or biotechnological potential of venom-derived compounds. Studying toxin absorption, distribution, metabolism, and excretion deepens our knowledge of predator-prey dynamics and underscores the importance of continued research into venom mechanisms and their broader implications.

Fig. 1.

Mechanisms of venom delivery in venomous species, The figure highlights the deployment of venom by venomous species through specialized structures, organs, or glands, and tissues (Created with BioR ender.com).

2.1. Snakes

Reptilian venoms, particularly those of cobras and vipers, contain diverse bioactive constituents with potent physiological effects [4]. Their activity, onset, target specificity, and therapeutic potential are profoundly shaped by molecular weight, which governs both the mechanism of action and biomedical applicability [5]. Snake venoms are complex mixtures comprising high-molecular-weight (HMW) toxins such as Cobra Venom Factor (CVF) from Naja kaouthia [6], L-amino acid oxidase (LAAO) from Pseudechis australis [7], α-neurotoxin (atratoxin) from Naja naja, and BjussuMP-II metalloproteinase from Bothrops jararacussu [8]. Enzymatic components, including snake venom metalloproteinases (SVMPs), serine proteases (SVSPs), and phospholipase A₂ (PLA₂), mediate haemorrhage via basement membrane degradation, disrupt coagulation pathways, interfere with platelet aggregation, lyse erythrocytes, and elicit pronounced inflammatory, myotoxic, and neurotoxic effects. Additional molecules such as thrombin-like enzymes (SVTLEs), disintegrins, β-defensin-like toxins, Kunitz-type inhibitors, cystatins, and bradykinin-potentiating peptides (BPPs) further diversify venom activity, underscoring their importance as templates for therapeutic innovation.

Three-finger toxins (3-FTXs) impair neuromuscular transmission primarily by inhibiting acetylcholinesterase and blocking acetylcholine receptors [9], while hyaluronidases enhance venom diffusion by degrading extracellular matrix components [10]. Snakes possess highly specialised venom-delivery systems comprising paired venom glands located behind the eyes and channels secreted venom through ducts into hollow or grooved fangs, which function as hypodermic injection apparatuses [11]. Elapids such as cobras and mambas possess elongated, often hinged fangs enabling deep tissue penetration and efficient envenomation [12]. Upon biting, pressure-driven mechanisms facilitate rapid venom injection. Venom composition and pathophysiological effects vary markedly among species. Elapid venoms are predominantly neurotoxic, blocking ion channels or neurotransmitter receptors and resulting in flaccid paralysis [13], whereas viperid venoms are chiefly hemotoxic, with metalloproteinases inducing vascular damage, haemorrhage, coagulopathy, and progressive tissue necrosis [14]. Cytotoxic and myotoxic components frequently compound both local tissue destruction and systemic toxicity [15].

2.2. Scorpion

Venomous arachnids such as Vietnam forest scorpions use their venom primarily to immobilise prey or for defence. Unlike organisms that rely solely on fangs, scorpions possess a specialised telson at the tip of the tail, containing paired venom glands that deliver venom through a sharp, curved aculeus. During a sting, muscular contractions regulate both the quantity and type of venom released, ranging from a mild pre-venom for deterrence to a potent venom for subduing prey [16], [17]. Scorpion venom is chemically diverse, encompassing several high-molecular-weight toxins, including Bengaline from Heterometrus bengalensis [16], BmHYA1 from Mesobuthus martensi Karsh [18], Heteroscorpine-1 (HS-1) from Heterometrus laoticus [19], and Discreplasminin from Tityus discrepans [20]. Functional studies show additional neurotoxicity, with Bothriurus bonariensis venom modulating voltage-gated sodium channels [21], and Tityus bahiensis venom enhancing acetylcholine release by prolonging action potentials [22]. Beyond neurotoxicity, scorpion venom activates macrophages and neutrophils, triggering inflammatory cytokine cascades that may progress to pulmonary oedema or death [23]. Cardiotoxic and myotoxic effects arise from components such as Imperatoxin I, a PLA2 that disrupts ryanodine receptor channels [24] like calcins, which act as ryanodine receptor agonists [25], and potassium-channel blockers like BeKm-1 and BmTx3b. Collectively, these elements highlight the dual nature of scorpion venom as both a potent toxin and a valuable source of therapeutic leads.

2.3. Spider

Venomous arachnids, including Brazilian brown recluse spiders, employ venom for predation and defence [26]. Spider venoms are highly complex cocktails of neurotoxins, proteolytic enzymes, and cytotoxic molecules with specialised biological activities. Neuroactive toxins such as α-, β-, γ-, δ-, and ε-latroinsectotoxins and latrotoxins from Latrodectus mactans tredecimguttatus and Latrodectus geometricus target neuronal pathways [27], [28]; while serine proteases from Loxosceles intermedia exhibit gelatinolytic activity responsible for the characteristic dermonecrosis following recluse bites. Additional potent components include δ-hexatoxin from Atrax robustus [29], which causes massive neurotransmitter release and can be fatal, and Magi 1–6 from Macrothele gigas, which disrupt sodium channels and impair neuronal signalling [30]. Acylpolyamines interact with glutamatergic and nicotinic receptors to induce paralysis [31], whereas cysteine-knot peptides modulate voltage-gated sodium channels [32], α-Latrotoxin from black widow spiders forms homotetrameric pores in presynaptic membranes, driving uncontrolled Ca²⁺ influx and excessive neurotransmitter release, often resulting in severe systemic toxicity [33]. Other key venom constituents include sphingomyelinase D, which triggers necrosis and inflammatory responses, and hyaluronidase, which facilitates venom diffusion through tissues [33], [34]. Venom delivery occurs via hollow fangs (chelicerae) connected to cephalothoracic venom glands [35]; muscular contractions inject venom into prey or perceived threats. Although composition varies widely across species, neurotoxic venoms (e.g., Latrodectus spp.) primarily target ion channels and neurotransmission [27], while necrotic venoms (e.g., Loxosceles spp.) induce profound tissue destruction [26]. Some species, such as tarantulas, possess venoms with strong myotoxic and cytotoxic activity to rapidly immobilise prey [35]. Spider venom use is further refined by adaptive strategies aligned with the venom optimisation hypothesis, allowing spiders to modulate venom volume and composition based on prey size, threat level, and metabolic cost. Synthesised within specialised secretory cells and delivered through highly efficient biomechanical systems, spider venoms represent an evolutionarily sophisticated tool optimised for maximal predatory and defensive effectiveness.

2.4. Honey-bee

Insects such as honeybees use venom primarily for defence, with species like the bullet ant capable of inducing extreme pain [36]. Bee venom from Apis mellifera is a complex mixture of peptides, enzymes, and proteins with diverse biological effects [37], [38]. Major constituents include allergens such as Api m 12 [38], [39]; and Major Royal Jelly Proteins (MRJP 1–9) [40], along with bioactive peptides including apamin [41], and secapin [42]. Envenomation triggers local inflammation, allergic reactions, and, in susceptible individuals, anaphylaxis [38]. Melittin, the dominant peptide, induces pain by activating TRPV1 channels and forming membrane pores [43], while phospholipase A2 (PLA2), though non-toxic alone, synergistically enhances haemolysis with melittin [44]. Apamin blocks Ca²⁺-activated K⁺ channels [41], mast-cell degranulating peptides promote histamine release (but may inhibit it at higher doses) [45], and hyaluronidase facilitates toxin spread by degrading extracellular matrix components [46]. Honeybees deliver venom through a barbed stinger connected to a venom gland. After penetration, the stinger anchors into the skin, allowing continued venom injection via muscular contractions even after the bee detaches, ultimately causing its death [47]. Melittin disrupts cellular membranes, causing pain, edema, and tissue injury, while PLA2 amplifies phospholipid degradation and immune activation [48]. Biogenic amines such as histamine contribute to swelling and hypersensitivity, and sensitised individuals may experience severe systemic reactions, including life-threatening anaphylaxis [38].

2.5. Jellyfish

Marine species such as box jellyfishes produce highly potent venoms capable of causing severe physiological reactions or death [49]. Jellyfish venoms contain diverse bioactive molecules, including Jellyfish Tentacle Extract (JFTE) from Aurelia aurita [50]. Key toxins include CfTX-1 and CfTX-2 from Chironex fleckeri [51]; CfTX-A and CfTX-B; CARTOX from Nemopilema nomurai [52]; and Letoxcn from Cyanea nozakii [53]. Metalloproteinases in N. nomurai venom induce dermatitis by disrupting cell junctions and immune cell adhesion [54] and cause myotoxicity through muscle penetration and fibre necrosis [55]. Serine proteases from the same species show fibrinolytic and anti-inflammatory effects [56]. Chironex fleckeri venom exerts cardiotoxicity by enhancing Na⁺ influx and causing Ca²⁺ overload in cardiac cells [57], with ATP2B1 mediating the cytotoxic response [58]. CfTX-A and CfTX-B also display potent hemolytic, pore-forming activity similar to Cry insecticidal toxins, aiding rapid prey immobilisation [59]. Cubozoans possess highly evolved venom systems delivered through nematocysts, specialised stinging organelles within cnidocytes, that eject a harpoon-like tubule within microseconds to inject venom [60], [61]. Although previously thought to be produced only near nematocysts, recent work on Alatina alata shows that gastric cirri gland cells also synthesise toxins, indicating a more distributed venom-production system [62]. Neurotoxins from species such as C. fleckeri disrupt ion channels, causing intense pain, paralysis, cardiovascular collapse, and systemic toxicity, while hemotoxins interfere with coagulation and circulation, worsening envenomation outcomes [53], [60].

2.6. Frog

Venomous mammals are rare, represented primarily by the platypus, with its venomous spurs, and a few shrew species capable of delivering venom through their bite. Although frogs are not traditionally classified as venomous, several species produce potent toxins that serve venom-like functions in predation or defence. Frog venoms contain diverse high-molecular-weight (HMW) toxins with notable biological effects. These include saxiphilin from Lithobates catesbeianus [63]; KPHTI from Kaloula pulchra hainana [64]; Bv8-AJ from Amolops jingdongensis [65]; hemolysin from Bombina variegata [66]; PSKP-1 and PSKP-2 from Phyllomedusa sauvagii [67]; and BPTI-family peptides from Dyscophus guineti [68]. Bv8 proteins in Bombina species stimulate ileum contractions in guinea pigs and induce hyperalgesia in rat models [69]. Batrachotoxin produced by Phyllobates frogs targets voltage-gated sodium channels, causing sustained activation that leads to muscle contraction, convulsions, and respiratory paralysis [70]. Similarly, toad venom from Rhinella schneideri contains cardiotonic heterosides that inhibit Na⁺/K⁺-ATPase, resulting in cardiotoxic and neurotoxic effects [71]. Poison dart frogs exemplify toxin-based defence, secreting potent skin alkaloids that rapidly penetrate oral and mucosal tissues of predators, causing swelling, nausea, paralysis, or death [72].

2.7. Sea slug

Venoms of sea slugs such as Pleurobranchus forskalii and Pleurobranchaea maculata contain low-molecular-weight (LMW) toxins like ergosinine and tetrodotoxin [73], [74], while Peronia peronii produces the high-molecular-weight (HMW) toxin Dolabelanin-b2 [74]. These compounds significantly enhance venom potency, exhibiting neuroactive effects relevant to chronic pain management and strong antibacterial activity. Sea slugs employ sophisticated chemical defence systems derived from their prey, metabolically modified dietary compounds, or de novo synthesis. These toxins are often paired with aposematic colouration and concentrated in exposed structures, mantle, foot, gills, rhinophores, or released via mucus, ink, and specialised mantle dermal formations (MDFs) [75]. Across habitats, these strategies serve as consistent and effective predation deterrents. Several sea slugs, particularly Glaucus and Phyllodesmium species, display unique adaptations that allow them to harness toxins from their prey. Glaucus atlanticus preys on venomous cnidarians such as Physalia physalis and sequesters undischarged nematocysts within its cerata, discharging them defensively when threatened. Phyllodesmium species similarly absorb toxic coral metabolites for chemical protection [76]. The venom effects mirror those of the prey toxins; cnidarian-derived venoms often contain neurotoxins and cytolysins that disrupt ion channels, causing paralysis and tissue damage [77].

2.8. Cone snail

Cone snail venom comprises a diverse array of bioactive toxins, including achacin from Achatina fulica [78]; ACE-1 from Conus purpurascens and ECE-1 from Conus ermineus [79]; conotoxins from Conus taeniatus [80]; and peptides Dis41 and Dis63 from Conus geographus, C. marmoreus, and C. distans [81]. The extreme potency of cone snail venoms is largely due to disulfide-rich conotoxins, which exhibit exceptional specificity toward ion channels and receptors. For example, µ-conotoxin SxIIIC selectively inhibits NaV1.7 sodium channels [82], SmIIIA and KIIIA target distinct channel subtypes [83], δ-conotoxin TxVIA inhibits T-type CaV3.1 channels [84], and α-conopeptide Eu1.6 targets N-type CaV2.2 channels [85]. Both high- and low-molecular-weight toxins in cone snail venom offer substantial therapeutic potential: HMW toxins for antibiotic and biopharmaceutical development, and LMW conotoxins owing to their exquisite receptor selectivity for pain management and peptide-based therapeutics. These molecules also illuminate disease mechanisms, predator-prey dynamics, and evolutionary adaptation, and serve as precise diagnostic and molecular probes. Cone snails use a specialised predatory mechanism in which a harpoon-like radular tooth connected to the venom apparatus is rapidly fired from the proboscis to inject venom within milliseconds. Typically buried in sand, they strike to detect prey with this hollow, syringe-like structure, delivering venom via muscular contractions of the venom duct [85]. This rapid immobilisation reflects the highly refined evolutionary design of cone snail predation [81].

3. Venom pharmacokinetics: understanding venom action

Pharmacokinetics is the study of the absorption, distribution, metabolism, and excretion of the compound by the body upon administration. Upon envenomation, the venom's components enter the bloodstream and quickly spread to different tissues. The rate at which the venom components get distributed in the body is highly influenced by the distribution rate and extent influenced by factors such as molecular size, lipid solubility, and binding affinity to plasma proteins. Metabolism mainly takes place in the liver, where enzymes like cytochrome P450 are essential for detoxifying venom toxins [86]. These enzymatic reactions can alter venom components, decreasing their toxicity and aiding in their excretion via the kidneys [87]. Understanding the pharmacokinetics of venom is crucial for creating effective antivenoms and treatments, as it offers insights into the duration and intensity of venom's physiological effects, helping manage envenomation cases. Decades of research have documented the pharmacokinetic properties of venom from snakes, scorpions, spiders, honey bees, frogs, jellyfishes, and cone snails.

The pharmacokinetics of various snake venoms and their isolated toxins have been studied in species including Naja naja atra [88]; Naja sumatrana [89]; Naja sputatrix [90], Bathrops alternatus[91]; Trimeresurus flavoviridis [92]; Cryptelyrops purpureomaculatus [93]; and Agkistrodon halys ussuriensis [94]. Pharmacokinetic profiles have been documented through various parenteral routes using techniques like ELISA and RIA. An in-depth analysis of the pharmacokinetics across various snake species, identified a two-compartment model for venom distribution characterized by an initial rapid distribution phase, followed by a slower terminal phase, where the venom swiftly disperses from the bloodstream to tissues, displaying low clearance and a high distribution volume [95]. Further research on intramuscular and subcutaneous administration routes revealed an initial absorption phase followed by slow elimination, with venom absorption as the rate-limiting step, potentially leading to localized tissue damage [96]; and a meta-analysis of human pharmacokinetics suggested a one-compartment model with an elimination half-life of approximately 10 h as the best fit [95]. Recently, a population pharmacokinetics model developed to describe the disposition of Pseudechis porphyriacus snake venom, a finding indicating that the kinetic profile followed a one-compartment model with first-order absorption and elimination [97].

Over the years, studies have documented the pharmacokinetics and biodistribution of venom from various scorpion species, including Androctonus amoreuxi [98]; Leiurus quinquestriatus, Buthotus judaicus [99]; and Hemiscorpius lepturus. Similar to snake venom profiles, scorpion venoms followed a two-compartment open system with rapid distribution and slow elimination. The uptake of venom by tissues was quick, with a distribution half-life ranging from 4 to 7 min and an elimination half-life ranging between 4.2 and 13.4 h [100]. Additionally, it was found that the uptake of venom by each organ varied based on the route of administration, highlighting its significance in the venom's pharmacokinetic profile [95]. To date, the pharmacokinetics of bee venom profiles have not been extensively studied. The pharmacokinetics of a new composition bee venom (NCBV) containing 76.2 % bee venom PLA2 (bvPLA2) demonstrated that bvPLA2 exhibits non-linear pharmacokinetics when administered subcutaneously at various doses [101]. No differences were observed in the pharmacokinetic profile when multiple doses were compared to a single-dose study. Additionally, other venom constituents did not alter the pharmacokinetic profile of bvPLA2. The tissue-to-plasma ratio was less than one at various time points, indicating limited tissue distribution of bvPLA2.

The pharmacokinetics of bufadienolides, a key component of toad venom and an active compound in Shexiang Tongxin Dropping Pill (STDP) have been extensively studied. Upon oral administration of STDP in rats, bufadienolides were swiftly absorbed and preferentially distributed to the heart and liver, showing a dose-dependent increase in the area under the curve. In ischemia-reperfusion models, plasma concentrations were notably lower while tissue concentrations were elevated compared to healthy controls [102]. In a parallel study, the pharmacokinetics of Caerin 1.9, a peptide derived from the skin secretions of the Australian tree frog, were examined [103]. The findings revealed that Caerin 1.9 exhibited rapid clearance from plasma, resulting in a short circulation time and elimination half-life, with limited distribution to organs and tissues, likely due to peptide degradation. Several pharmacokinetic studies have been conducted on toxic peptides from cone snails. Contulakin-G (CGX-1160), a synthetic peptide from the Conus geographus snail, demonstrated a bi-exponential disposition in cerebrospinal fluid following intrathecal administration. It showed a rapid rate constant that was significantly higher than the slow rate constant, with the slow rate constant exhibiting nonlinear dose dependence [104]. Similarly, SNX-111, an omega conopeptide neuronal calcium channel blocker, showed a steady-state concentration within 2 h post-infusion following constant rate intravenous administration in rats and cynomolgus monkeys. Its elimination profile displayed a two-component model with an initial fast component and a slow terminal half-life [105]. These studies highlight the diversity in venom pharmacokinetics, which is crucial for understanding how molecular weight variations in venom toxins affect their interaction mechanisms. The distinct roles of low and HMW toxins, such as enzyme inhibition or membrane disruption, underscore the need to explore how these factors contribute to the physiological responses in both prey and predators, informing more effective therapeutic interventions.

4. Apitherapy: ancient venom therapies

Venom has a long history in medicine, from ancient remedies to modern therapies. Historically used for various ailments, its potent properties have led to contemporary research uncovering its therapeutic benefits. Animal venoms, with their diverse bioactive compounds, are being explored for their potential in adjunctive or alternative therapies, including cancer, diabetes, and cardiovascular diseases [1]. Their unique peptides target specific molecular components, offering promising avenues for pharmaceutical research. In Ayurveda, animal venoms (e.g., from snakes and scorpions) have traditionally been used for medicinal purposes, particularly for their anti-inflammatory and neuroprotective properties [106]. The "Charaka Samhita" mentions venom in the context of "Visha Chikitsa" (toxicology), detailing its therapeutic applications when prepared and administered according to Ayurvedic principles [107]. Historically, venom has been used to alleviate joint pain and treat wounds by promoting tissue regeneration and reducing infection [53], [108]. Modern research continues to explore venom's potential, including its use in cancer treatment. Table I outlines the diverse proteinaceous toxins derived from venomous species, underscoring their therapeutic applications.

Table I.

Proteinaceous toxins derived from venomous species and their therapeutic applications.

Species	Name	Toxin	Applications	References
Snake	Ophiophagus hannah, Agkistrodon acutus, Bungarus fasciatus, Bothrops atrox, Lachesis muta, Agkistrodon halys	L-amino acid oxidase LAAO	Anti-tumor	[109]
	Naja kaouthia	Cobra venom factor (CVF)	Anticomplement activity	[110]
	Pit vipers, boomslang and twig snakes	Snake venom hyaluronidases (SVHYA)	Adjuvant for antivenom production	[111]
	Bothrops atrox	Snake venom thrombin-like enzyme (SVTLE)	Therapeutic agents to treat haemostatic disorders	[112]
	Hoplocephalus stephensii	Hopsarin D	Procoagulant and in vitro post-synaptic neurotoxic activity	[113]
	Lachesis muta muta	Kallikrein-like proteinase	Lowers blood pressure in experimental rats	[114]
	Naja nivea	Three-finger toxin (3FTx), phospholipase, & Cysteine-rich secretory proteins (CRISP)	Production of an effective antivenom	[115]
	Bothrops jararacussu	BjussuMP-II	Inhibitory effects on platelet aggregation	[116]
Scorpion	Heterometrus bengalensis Koch	Bengaline	Antiproliferative and apoptogenic activity	[117]
	Buthus martensi	BmHYA1	Capacity to digest a wide range of hyaluronan fragments	[118]
	Tityus discrepans	Neopladines 1 and 2	Apoptotic activity on SKBR3 human breast carcinoma cells	[119]
	Anuroctonus phaiodactylus	Phaiodactylipin	Anticoagulant activity	[120]
	Pandinus imperator	Imperatoxin (IpTxi)	Exhibits phospholipase activity	[121]
	Heterometrus laoticus	Heteroscorpine-1 (HS-1)	Anti-nociceptive and anti-inflammatory activity	[122]
	Tityus discrepans	Discreplasminin	Anti-fibrinolytic activity	[123]
	Mesobuthus tamulus	ButaIT	Insecticidal agents	[124]
Spider	Latrodectus mactans	α, β, γ, δ, and ε-LIT	Insecticidal agents	[125]
	Latrodectus tredecimguttatus	Latroeggtoxin-I	Exhibits antibacterial activity	[126]
	Loxosceles intermedia	Serine proteases	Gelatinolytic activity	[26]
	Loxosceles intermedia, Loxosceles laeta, and Loxosceles gaucho	Astacin-like Metalloprotease (LALPs)	Gelatinolytic activity	[127]
	Latrodectus tredecimguttatus	α-Latrotoxin	Treatment of diabetes mellitus and obesity	[128]
	Macrothele gigas	Magi 1–6	Affecting sodium ion channels	[129]
	Atrax robustus	δ-hexatoxin	Neurotransmitter release	[130]
	Apis mellifera	Api m 12 and Ves v 6	Contributes to venom immunotherapy	[131]
	Apis mellifera	Api m 2	Contributes to allergen immunotherapy	[132]
	Apis mellifera	MRJP 1	Anti-proliferative activity	[133]
	Apis mellifera	MRJP 1–9	Antimicrobial activity, immuno-modulatory, anticarcinogenic activity	[134]
	Apis mellifera	Phospholipase A2 (PLA2)	Synergistic reaction with melittin in mammal erythrocyte lysis process	[135]
	Apis mellifera	Apamin	Anti-atherosclerotic activity	[136]
	Apis mellifera	Melittin	Anti-cancer activities	[137]
	Apis mellifera	Tertiapin	Prevents atrioventricular transmission	[138]
	Apis mellifera	Secapin	Anti-elastolytic activity	[139]
	Apis mellifera	Adolapin	Anti-nociceptive activity	[140]
Jellyfish	Aurelia aurita	Jellyfish Tentacle Extract (JFTE)	Anticoagulant activity	[141]
	Nemopilema nomurai	CARTOX	Possess haemolytic activity	[142]
	Cyanea nozakii	Letoxcn	Development of targeted treatments (antivenoms)	[143]
	Chironex fleckeri	CfTX-1 and CfTX-2	Dermonecrotic activity	[144]
	Chironex fleckeri	CfTX-A and CfTX-B	Affect the cardiovascular system	[145]
	Rana catesbeiana	Saxiphilin	Acts as a ‘toxin sponge’ involved in toxin resistance	[146]
Frog	Kaloula pulchra hainana	KPHTI	Trypsin inhibitory activity	[147]
	Amolops jingdongensis	Bv8-AJ	Wound healing regulator	[148]
	Rana catesbeiana	Ranatuerin-1	Displays antimicrobial activity	[149]
	Phyllomedusa sauvagii	PSKP-1 and PSKP-2	Inhibits serum prolyl endopeptidase	[150]
	Dyscophus guineti	BPTI family peptide	Protease inhibitor	[151]
	Discodoris boholensis	Protein	Functional food and medicine	[152]
Sea slug	Peronia peronei	Dolabelanin-b2	Antimicrobial activity	[153]
	Pleurobranchus forskalii	Ergosinine	Understanding and modulating venoconstriction	[154]
	Pleurobranchaea maculata	Tetrodotoxin	Dietary source	[155]
	Achatina fulica	Achacin	Antimicrobial activity	[156]
Snail	Conus purpurascens and Conus ermineus	Angiotensin-converting enzyme-1 (ACE-1) & Endothelin converting enzyme-1 (ECE-1)	Enhancement of neurotrophic peptide toxin activity	[157]
	Conus geographus	μ-conotoxins	Analgesic activity	[158]
	Conus arenatus, Conus coronatus, Conus ebraeus, Conus imperialis, Conus lividus, Conus marmoreus, Conus quercinus, Conus rattus, Conus sponsalis, Conus varius, and Conus virgo	Conoporin	Biomedical applications & drug development	[159]
	Conus villepinii	Conopressin-S	Act as neurotransmitters	[160]

Snake venom, particularly batroxobin from Bothrops moojeni, is valuable for its diverse biochemical properties and potent activities. Batroxobin is used as a topical hemostatic agent in spinal and cardiovascular surgeries and has shown neuroprotective effects by blocking the Sirt1 pathway and preventing astrocyte activation in traumatic brain injury [108]. A study found patients suffering from profound sudden sensorineural hearing loss (SNHL) over 100 dB HL when treated with batroxobin showed a greater reduction in auditory threshold and overall improvement compared to those who did not receive it [161]. In another study, collinein-1 (a serine protease) from Crotalus durissus collineatus, produced using recombinant technology demonstrated blockage of hEAG1 ion channelled in Pichia pastoris [162]; an inhibition significantly reducing cell viability in the hEAG1-overexpressing MCF7 breast cancer cell line.

Scorpions, members of the class Arachnida, have existed and evolved for around 400 million years. Historically, their highly toxic venom has been used for medical purposes in various Asian and African countries, including Egypt and Pakistan. Scorpion peptides, known for their diverse biological activities, have gained attention in biotechnology and medicine. The complex blend of peptides and proteins in scorpion venom, evolved for prey capture and predator defence, has spurred interest in identifying its therapeutic components. Chlorotoxin, a small peptide from the venom of the deathstalker scorpion (Leiurus quinquestriatus), inhibits chloride channels and binds to specific receptors on cancer cells. It shows promise for imaging and treating glioma, a type of brain tumor [163]. Scorpine, extracted from Pandinus imperator venom, has antibacterial properties against bacteria and fungi and enhances immune function by boosting phagocytosis and cytokine production, potentially leading to new antibacterial drugs and immunotherapies [164]. Additionally, the scorpion-derived peptide BmKn2-T5 exhibits promising antiviral activity against EV71 and other enveloped viruses, suggesting its potential as a therapeutic candidate [165]. Spider venom compounds, especially those with an inhibitor cystine knot (ICK) structure, exhibit diverse pharmacological effects, including antibacterial, anticancer, neuroprotective, and antinociceptive properties, indicating significant therapeutic potential [166]. For instance, the disulfide-rich peptide Hila from the Australian funnel-web spider (Hadronyche infensa) shows strong neuroprotective effects in ischemic stroke models, reducing brain damage and offering potential for neuroprotective drug development [167]. Moreover, HwTx-IV (Hanatoxin-IV), a peptide toxin derived from the tarantula Grammostola spatulata, serves as a potent inhibitor of voltage-gated potassium (Kv) channels. Research indicates that an N-terminal pyroglutamate-modified version of HwTx-IV exhibits superior blocking efficacy compared to its glutamate-containing counterpart. This variant demonstrates strong and sustained binding activity in DRG neurons and HEK293 cells expressing NaV1.7, especially under high depolarizing conditions [168].

Bee venom, or apitoxin, shows therapeutic promise in treating various cancers, including liver, lung, prostate, bladder, kidney, and breast cancers, due to peptides like melittin and PLA2. These peptides can cross the blood-brain barrier, making them potential candidates for central nervous system malignancies [169]. Bee venom also modulates the NF-κB pathway to reduce amyloidogenesis, memory loss, and neuroinflammation, while melittin enhances neuroprotection and cognitive function by affecting the TrkB/CREB/BDNF and Nrf2/HO-1 pathways [170]. Bee venom toxins, Api m 12 from Apis mellifera, play a role in immunotherapy and desensitization for allergic individuals. MRJP 1–9 in honeybees are known for their nutritional benefits and therapeutic properties, especially their antimicrobial and anti-apoptotic effects [171]. In contrast, toxins such as melittin, apamin, tertiapin, and secapin exhibit potent biological activities, including anti-cancer, anti-atherosclerotic, and anti-elastolytic effects, while adolapin is known for its anti-nociceptive pain relief [172], [173], [174]. Despite their potential, further clinical research is required to assess their effectiveness, safety, and healthcare professionals should closely monitor appropriate dosing, and any therapeutic use due to the risk of severe allergic reactions.

Jellyfish venom toxins, such as JFTE from Aurelia aurita, exhibit significant anticoagulant activity, which could be valuable for medical treatments [175]. Toxins like CfTX-1 (43 kDa) and CfTX-2 (45 kDa) from Chironex fleckeri are known for their dermonecrotic effects, causing severe tissue damage. CfTX-A and CfTX-B from the same species affect the cardiovascular system, making them potential candidates for studying cardiovascular diseases [176]; while Letoxcn from Cyanea nozakii contributes to the development of targeted treatments such as antivenoms [177].

Frog-derived compounds highlight the intersection of natural biology and modern medicine. Bufotenin, a psychoactive compound from the Colorado River toad, and Magainins, antimicrobial peptides from the African clawed frog, showcase the potential of amphibian compounds [178]. Dermaseptins, another set of antimicrobial peptides, are promising for bacterial and viral infections [179]. Frog skin peptides, initially noted for antimicrobial or immunomodulatory effects, also stimulate insulin release, showing potential as incretin-based treatments for Type 2 diabetes [180]. Additionally, Cerulein, a potent peptide from tropical frog skin, exhibits strong digestive and analgesic properties [181]. Frog venom toxins exhibit diverse pharmacological properties with various therapeutic potential. Saxiphilin from Rana castesbeiana functions as a "toxin sponge," providing resistance against other toxins [182]. KPHTI from Kaloula pulchra hainana is recognized for its trypsin inhibitory activity, which has potential therapeutic applications [183]. Bv8-AJ from Amolops jingdongensis plays a role in wound healing regulation [184]; while Hemolysin from Bombina variegata shows notable antibacterial properties [185]. PSKP-1 and PSKP-2 from sauvagii inhibit serum prolyl endopeptidase, suggesting uses in peptide hormone regulation [186]. The BPTI family peptide from Dyscophus guineti acts as a protease inhibitor, crucial for biochemical processes and therapeutic applications [187]. Collectively, these toxins underscore the pharmacological diversity of frog venom, with applications ranging from antimicrobial and wound healing to protease inhibition and toxin resistance. Proteins from sea slug venoms, such as Paromoionchis tumidus, Dolabelanin-b2 from Peronia peronii, Ergosinine from Pleurobranchus forskalii, and Tetrodotoxin from Pleurobranchaea maculata, have potential applications in functional foods and medicines due to their bioactive properties [156,157,158]. These toxins exhibit significant antimicrobial activity, making them promising candidates for new antibiotic development. They also provide valuable insights into venoconstriction, contributing to cardiovascular research, and play a role in understanding toxin accumulation and safety in marine food chains. This highlights the diverse potential of sea slug venoms in medical therapies, antibiotic discovery, cardiovascular studies, and food safety [1]. Cone snails produce venom with diverse peptides called conotoxins, each with unique biological effects. Alpha-conotoxin Vc1.1 (ACV1) from Conus victoriae binds α9α10 nicotinic acetylcholine receptors and shows promise as an analgesic and neuroprotective agent, especially for neuropathic pain and neurodegenerative diseases [188]. Ziconotide, a synthetic form of ω-conotoxin MVIIA from Conus magus, blocks N-type voltage-gated calcium channels in neurons and is effective for severe chronic pain unresponsive to conventional treatments [189]. Conantokins and conotoxins are also being explored for Alzheimer's disease with modified conantokins potentially identifying NMDA receptors involved in localized brain damage and serving as protective agents [190]. Proteins such as Achacin from Achatina fulica, ACE-1, and ECE-1 from Conus purpurascens and Conus ermineus exhibit strong antimicrobial properties and enhance the activity of neurotrophic peptide toxins, highlighting their neuropharmacological potential [191]. Additionally, μ-conotoxins from Conus geographus, Conoporin from Conus taeniatus, Conopressin-S from Conus geographus and Conus striatus, and Dis41 and Dis63 from Conus distans are recognized for their potent analgesic properties and potential in pain management [192]. These toxins are also explored for their biomedical applications and drug development, functioning as neurotransmitters and offering insights into nervous system modulation. Their defensive roles further emphasize the ecological significance of these toxins.

5. Venom-based therapeutics: innovations and marketed formulations

5.1. Toxin mimicry: target identification in venom research

The power of toxin mimicry-mimicking venom toxins for therapeutic development, relies heavily on resolving the structures of toxin-target complexes [193]. Identifying targets is pivotal for understanding the precise molecular mechanisms by which venom toxins exert their effects. For example, hemotoxins have been instrumental in mapping the coagulation cascade due to the relative simplicity of this system [194]. Conversely, neurotoxins, which act on the more intricate and less understood human neurological system, pose a significant challenge for target identification [195]. Venom toxins, particularly neurotoxins, are invaluable leads for developing drugs targeting ion channels, representing nearly 20 % of current pharmaceutical targets, due to their roles in diverse physiological processes. However, ion channels' functional complexity, structural unknowns, and isoform diversity pose substantial obstacles for selective drug development. For instance, experimental screening becomes highly challenging when a venom toxin interacts with an unidentified target. A notable example is myotoxic phospholipase A2S (PLA2S), which bind to an unidentified membrane protein on muscle sarcolemma, the interaction localising their hydrolytic activity to muscle tissue. However, despite decades of research, the exact target remains elusive. Even after identifying a target, understanding the 3D structure of the toxin-target complex is critical. Without such structural knowledge, toxin mimicry must rely on less precise ligand-based design methods, which are inherently less efficient than structure-based drug discovery.

5.2. Computational chemistry: role in venom-based drug discovery

Advances in computational chemistry have opened new avenues for accelerating venom-based drug discovery. Advancements in computational power, coupled with artificial intelligence (AI) and deep learning, are transforming venom research by enabling protein homology modeling to predict the structures of unknown targets, facilitating protein-protein docking to simulate toxin-target interactions, leveraging computational mutagenesis techniques like alanine scanning to analyse structure-function relationships, and aiding enzymatic mechanism studies to elucidate biochemical pathways [196].

These methods are particularly valuable when a toxin exhibits promising bioactivity against an unidentified target. Computational tools can screen structural databases of known targets to predict toxin-target affinities, significantly narrowing potential candidates for experimental validation, while also delineating interacting regions between toxins and targets [197]. While homology modelling and docking may not always provide definitive answers, they guide experimental efforts by prioritising likely candidates. Determining the geometry of toxin-target complexes with atomic precision remains computationally challenging, especially when modelled structures are involved. A case in point is the collaborative use of toxin mimicry and computational approaches to uncover how venom components play a role in drug discovery.

5.3. Venomics: role of advanced “OMICS” technologies

The integration of computational and experimental approaches holds great promise for advancing target identification and toxin-based drug development. By combining computational insights with traditional medicinal chemistry, toxins can be optimised into small, bioavailable molecules while preserving their biological activity. Cutting-edge technologies such as proteomics, transcriptomics, and high-throughput functional assays have revolutionised venom research, enabling more precise drug discovery [198]. These approaches offer a deeper understanding of venom composition, evolution, and the molecular mechanisms underlying its toxicity, which supports the development of effective antivenoms [199]. Additionally, they expand our knowledge of biological processes in venom glands and facilitate the discovery of novel diagnostic and pharmacological agents. By elucidating the molecular complexity of venom components and their mechanisms, venomics has identified diverse venom peptides with great potential as templates for novel drug development targeting various diseases. These advancements continue to drive global efforts among toxinologists and clinicians in exploring venom-derived natural toxins for innovative therapeutic applications. Tam M Huynh et al. [200] used venomics to isolate and characterise two neurotoxins, α-Elapitoxin-Nn2a and α-Elapitoxin-Nn3a, from Indian cobra venom, revealing structural differences and inhibitory effects on nicotinic acetylcholine receptors. Their study highlighted antivenom limitations, emphasising the need for targeted development. Similarly, Kuzmenkov et al. [201] resolved structural and pharmacological properties of apamin from Apis mellifera venom, demonstrating its selective inhibition of small-conductance Ca²⁺-activated K⁺ channels and its potential as a pharmacological tool and drug model. Keimasi et al. [202] applied venomics to investigate omega-lycotoxin-Gsp2671e from Loxosceles praegrandis spider venom, showing its neuroprotective effects in cognitive impairment models, including improved synaptic protein expression and memory restoration. Furthermore, Kimball et al. [203] explored μ-conotoxin KIIIA's interaction with the hNav1.7 pain channel, providing insights for pain management therapeutics, while T. N. T. Ho et al. [204] characterised αD-VxXXB, an allosteric blocker of nicotinic acetylcholine receptors from Conus vexillum, identifying its unique binding mechanism.

5.4. Venom-derived marketed formulations and their applications

Major pharmaceutical companies are increasingly prioritizing venom-based drug discovery, utilizing toxins to validate targets and develop treatments. Venoms, derived from creatures like snakes, spiders, scorpions, honey bees, jellyfish, sea slugs, and cone snails, contain a diverse range of bioactive compounds with distinct mechanisms of action. Advancements in drug delivery systems and biotechnology have further improved the efficacy and precision of venom-derived therapies. These innovations have enabled the development of new treatments for conditions such as chronic pain, autoimmune diseases, and cancer, marking a significant advancement in translational medicine. Fig. 2 presents a comprehensive overview of marketed formulations for treating diverse therapeutic conditions. Each entry includes detailed information such as the brand name, source of the formulation, therapeutic applications it targets, its mode of action, and molecular structures sourced from PubChem, providing a thorough understanding of their pharmaceutical characteristics and applications in clinical settings.

Fig. 2.

Venom-derived marketed formulations and their applications, The figure represents a comprehensive overview of marketed drugs derived from venomous species for treating diverse therapeutic conditions (Created with BioRender.com).

Venom-based drug discovery has revolutionized modern medicine, providing targeted and highly effective treatments for a diverse range of medical conditions. From cardiovascular diseases to neurodegenerative disorders, cancer, and chronic pain management, venom-derived compounds have demonstrated remarkable therapeutic potential. Drugs such as Aggrastat® (Tirofiban) and Integrilin® (Eptifibatide), sourced from snake venoms, function as potent antiplatelet agents, reducing the risk of clot formation and heart disease [205]. Similarly, Capoten® (Captopril), derived from Bothrops jararaca, is widely used as an ACE inhibitor for hypertension and heart failure management [206]. Beyond cardiovascular health, venom components have played a crucial role in pain relief and anti-inflammatory treatments. For instance, Apitox® (Apitoxin), extracted from bee venom, is utilized in rheumatoid arthritis therapy [207]; while Cobratide® (Cobrotoxin) from the Chinese cobra is employed for chronic pain management [208]. Additionally, non-opioid analgesics like Prialt® (Ziconotide), sourced from cone snails, have shown promise as alternative pain relief options, targeting N-type calcium channels without the risk of addiction [209].

In cancer therapy, venom-derived peptides have shown exceptional efficacy in inhibiting tumor progression and inducing apoptosis. Buformin® (Cinobufacin) from the Asiatic toad and TM601® (Chlorotoxin) from the Deathstalker scorpion are widely researched for their cytotoxic effects on cancer cells, particularly in glioblastomas [210], [211]. Similarly, Theranekron® (Theraphotoxin) from tarantulas has demonstrated potential in treating androgen-dependent prostate cancer through caspase-3 mediated apoptosis [212]. Beyond oncology, venom-derived therapies extend into rare disease treatment and antivenom production. Kalbitor® (Ecallantide), derived from viper venom, is used to treat hereditary angioedema [213]; while Viperfav® ((equine-derived F(ab')2 fragments) effectively neutralizes viper envenomation [214]. Advances in biotechnological applications of venomics continue to drive innovations in drug development, offering solutions to previously untreatable conditions. This seamless integration of nature's biochemical arsenal into modern medicine underscores the growing significance of venom-based therapeutics in shaping the future of healthcare. Though venom-derived therapeutics represent a promising frontier in drug discovery, leveraging bioactive molecules for innovative treatments from pain management to cancer therapy, translating venom components into clinically viable drugs presents several challenges, particularly in regulatory approval [1].

6. Regulatory hurdles

Developing venom-derived drugs is a complex, multi-step process designed to ensure safety, efficacy, and regulatory compliance. It begins with rigorous preclinical research, often involving animal models, to establish safety profiles and understand pharmacokinetics. A critical step in this process is identifying and characterizing the active ingredients within complex venom mixtures, which requires advanced analytical techniques [215]. Formulation development follows, focusing on creating a stable and effective drug by determining the optimal delivery method and ensuring the drug's stability and potency during storage and administration [216]. Despite these efforts, there remains a significant gap between the number of pharmacologically promising compounds derived from venoms and those that ultimately gain approval.

The preclinical evaluation of venom-derived drugs faces several challenges. Despite being rich in bioactive peptides, venom components often fail to meet the criteria for therapeutic application, such as selectivity, stability, and production cost. Optimisation of drug metabolism and pharmacokinetics is essential, but many toxins struggle to effectively cross key biological barriers, such as the blood-brain barrier, which hampers their therapeutic potential [217]. Additionally, the susceptibility of these peptides to degradation by blood proteases and their potential immunogenicity pose further challenges for their pharmaceutical use [218]. These issues prolong the preclinical phase, making it both costly and time-consuming. Regulatory hurdles, insufficient funding, and manufacturing difficulties further complicate the path from preclinical research to clinical trials.

One of the most significant challenges in venom-based therapeutics is the limited availability of venom from small or rare venomous species. For instance, the venom yield from the Cupiennius salei spider is as little as 10 μl, with regeneration requiring 8–16 days, making it difficult to conduct comprehensive studies [219]. In contrast, larger species like the Lachesis muta muta snake can produce milliliters of venom in a single milking, allowing for higher yields and a more straightforward path to toxin extraction [220]. The complexity of venom composition, including mucus-rich samples from toads and frogs, also presents challenges when employing omics technologies for in-depth analysis. Isolating specific toxins from such complex mixtures further hampers progress in basic toxin research.

Navigating the approval pathways for venom-derived drugs is often complicated due to the unique nature of these compounds. Intellectual property disputes, changes in program leadership, funding shortages, and business decisions frequently lead to the discontinuation of drug development programs. The lack of publicly available data on critical stages of drug development further complicates the process by obscuring key milestones and hindering progress [221]. Although efforts have been made to retrieve this information from scientific literature, the scarcity of available data remains a significant barrier, preventing complete transparency and impeding advancements in the field [222]. Fig. 3 depicts the sequence of processes needed during the inspection of a release drug.

Fig. 3.

Standard procedures and the sequential process necessary during the inspection, The figure highlights the standard procedures and essential steps involved in the inspection process (Created with BioRender.com).

Regulatory submissions represent a critical phase in the approval process, starting with an Investigational New Drug (IND) application, which includes preclinical data and proposed clinical trial designs. This is followed by Phase I, II, and III clinical trials to assess the drug’s safety, efficacy, dosage, and potential side effects in human subjects [223]. Phase III trials, involving larger populations, are particularly crucial for demonstrating efficacy, after successful trials of which New Drug Application (NDA) or Biologics License Application (BLA) is submitted for regulatory review, encompassing all preclinical and clinical data. Post-market surveillance continues to monitor the drug’s safety and effectiveness in broader patient populations, potentially leading to further safety updates or labelling changes.

The development of venom-derived therapeutics faces several additional challenges, including variability in venom composition, the potential for allergic reactions, and the need for specialized manufacturing processes to ensure product consistency and purity. The complexity is further heightened by the need to navigate diverse global regulatory requirements, necessitating tailored strategies for different markets. Overcoming these hurdles requires strong collaboration among pharmaceutical companies, academic researchers, and experts in venom biology and toxicology [224].

Moreover, the international “Access and Benefit Sharing (ABS)” agreement under the Convention on Biological Diversity provides a legal framework for the equitable access, transfer, and utilization of genetic resources [225]. Enforced across 131 countries, the Nagoya Protocol establishes guidelines for biodiversity governance, ensuring that benefits from genetic resources and traditional knowledge are shared fairly. The protocol mandates prior informed consent and mutually agreed terms for accessing genetic resources, encouraging conservation and sustainable use while ensuring that the benefits reach the countries providing these resources. In India, regulatory authorities overseeing venom-related activities, including the production of antivenoms and venomous animal research, play a crucial role in ensuring the safe and effective development of venom-derived therapeutics. Table II outlines the regulatory bodies responsible for venom-related activities both in India and abroad.

Table II.

Global and Indian venom and antivenom regulatory bodies.

Organization	Description	References
Global Regulatory Bodies
World Health Organization (WHO) - Asia, Africa, America, Europe	Support global health initiatives for venom-derived drugs via a dedicated program for drug envenoming	[226]
Food and Drug Administration (FDA) -USA	Regulates and approves US medicines, including venom-derived drugs, by evaluating clinical data and overseeing manufacturing	[227]
European Medicines Agency (EMA) -Netherlands	Regulates EU medicinal products, including venom-derived drugs, ensuring safety, efficacy, and quality through scientific evaluations	[228]
Health Canada - Canada	Regulates pharmaceuticals in Canada, including venom-derived drugs, by assessing safety, efficacy, and quality	[229]
Therapeutic Goods Administration (TGA) - Australia	Oversees the regulation of venom-derived medicines in Australia	[230]
Medicines and Healthcare products Regulatory Agency (MHRA) - United Kingdom	Regulates UK venom-derived medicines to ensure they meet US standards	[231]
National Institute for Biological Standards and Control (NIBSC) - United Kingdom	Sets standards for biological products, including venom, to ensure quality and consistency	[232]
International Society on Toxicology (IST) - Asia, Africa, America	Promote research and development in venom and venom-derived therapeutics	[233]
Indian Regulatory Bodies
Central Drugs Standard Control Organization (CDSCO)	Regulate and approve drugs and biologics, including antivenoms, ensuring safety, efficacy, and quality	[234]
Indian Pharmacopoeia Commission (IPC)	Set and enforce drug standards, including for antivenoms, to ensure quality, purity, and effectiveness	[235]
National Centre for Disease Control (NCDC)	Implement NAPSE to reduce snakebite deaths and disabilities by 50 % by 2030	[236]
National Bee Board (NBB)	Advance beekeeping by supporting R&D, ensuring quality, and fostering market growth	[237]
Department of Science and Technology (DST)	A Ministry of Science and Technology agency researching and innovating venom-based therapeutics	[238]
Indiansnakes	Provide resources for understanding and managing venomous snake interactions in India, promoting safety, conservation, and education	[239]

7. Conclusions

The evolution of venom to a promising therapeutic tool exemplifies the potential of natural toxins in modern medicine. This review highlights how venomous substances, traditionally linked to harm, which were originally used for host defence and prey digestion, are now being recognized as valuable medicinal agents through advanced research and innovative drug development. By exploring the diverse mechanisms of venom deployment and their interaction with human physiology, we reveal the intricate processes underlying venom transformation into effective treatments. The ongoing advancements in venom research highlight these complex biochemical mixtures' vast, untapped potential, which continue to offer new opportunities for therapeutic interventions. However, challenges such as regulatory barriers and incomplete understanding of venom functions must be addressed to realize their medical benefits fully. As we continue to bridge the gap between venomous toxins and medicine, the future of venom-derived therapeutics promises to unlock new avenues for treating chronic diseases and enhancing healthcare outcomes.

CRediT authorship contribution statement

Sanskruti Shrenik Patil: Writing – original draft, Visualization, Data curation. Akshatha Ganesh Nayak: Writing – review & editing. Raghu Chandrashekhar Hariharapura: Writing – review & editing, Resources, Conceptualization. Debalina Bose: Writing – original draft, Methodology, Conceptualization. Kishore Srinivasan: Writing – review & editing, Writing – original draft, Visualization, Data curation.

Funding

Open access funding is provided by Manipal Academy of Higher Education, Manipal.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling Editor: Lawrence Lash

Data availability

No data was used for the research described in the article.