Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications
Abstract
1. Introduction
2. Results
3. Discussion
3.1. Geographic Distribution of Snake Venom-Related Patents
3.2. Ten-Year Range Patent Distribution
3.3. Most Used Snake Species in Pharmacological Innovations
Family | Scientific Name | English Common Name | Pharmacological Activity Reported in Literature | Reference |
---|---|---|---|---|
Pit Viper | Agkistrodon piscivorus piscivorus | Northern Cottonmouth | Antithrombotic | [24] |
Bothrops atrox | Fer-de-Lance, common lancehead | Anticoagulant | [25] | |
Crotalus adamanteus | Eastern Diamondback Rattlesnake | Anticancer | [26] | |
Crotalus durissus terrificus | South American rattlesnake | Anticancer, antimicrobial | [27] | |
Gloydius intermedius | Central Asian pitviper | Anticoagulant and antiplatelet | [28] | |
Protobothrops mucrosquamatus | Brown spotted pitviper | Anticoagulant and antiplatelet | [29] | |
Trimeresurus fasciatus | Banded Pit Viper | Anticoagulant | [30] | |
Trimeresurus stejnegeri | Chinese Green Tree Viper, Stejneger’s Bamboo pitviper | Virucidal activity | [31] | |
Viper | Cerastes spp. | – | Antiplatelet activity | [32] |
Daboia russelii | Russel’s Viper | Anticoagulant and antiplatelet | [33] | |
Deinagkistrodon acutus | Chinese Moccasin, Hundred-pace viper | Antithrombotic, Antiplatelet | [34] | |
Gloydius brevicaudus | Short-tailed Mamushi | Anticoagulant and antiplatelet | [28] | |
Gloydius ussuriensis | Ussuri Mamushi | Anticoagulant and antiplatelet | [28] | |
Elapid—Krait | Bungarus fasciatus | Banded Krait | Virucidal activity and Antibacterial | [25,31] |
Bungarus multicinctus | Many-banded Krait | Immunogenic and anti-inflammatory | [35] | |
Elapid—Cobra | Naja atra | Chinese Cobra | Anticoagulant | [36] |
Naja kaouthia | Monocled Cobra, Monocellate Cobra | Antiviral, neuromodulatory and analgesic activities | [25] | |
Naja melanoleuca | Central African Forest Cobra, Black and White Cobra | Antimicrobial and Antiviral | [37] | |
Naja naja | Common cobra, Spectacled cobra | Virucidal activity | [31] | |
Ophiophagus hannah | King Cobra | Analgesic | [25] | |
Elapid—Sea snake | Hydrophis cyanocinctus | Annulated Sea Snake, Dusky-chinned giant sea snake | Antimicrobial and Anti-Inflammatory Activity | [38] |
3.4. Therapeutic Indications, Applications, and Compounds Reported in Snake Venom Innovations
3.4.1. Anticoagulants and Hemostatic Agents
3.4.2. Metalloproteinases
3.4.3. Fibrinolytic Enzymes
3.4.4. Coagulation Factor Activators
3.5. Anti-Inflammatory Agents
3.6. Cancer Therapies
3.7. Cytotoxins and Polypeptides
3.8. Fusion Proteins
3.9. Pain Management
3.10. Antinociceptive Agents
3.11. Neurotoxins
3.12. Antimicrobial Agents
3.12.1. Antibacterial Agents
- Snake Venom Polypeptides
3.12.2. Anti-Viral Agents
- Broad-Spectrum Antivirals
3.13. Anti-Venom Innovations
- Neutralizing Anti-Venoms
3.14. Extraction and Stabilization Methods
4. Conclusions
5. Materials and Methods
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Systematic Review Registration Statement
References
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No | Cod. | Institution | Year/Country | Species | Active Compound | Activity and Mechanism | Administration Route | Dose | Assay |
---|---|---|---|---|---|---|---|---|---|
1 | CN105567666 (A) | Pharmaceutical industry | 2016/China | Naja atra | PIII type metalloproteinase | Anticoagulant: The target protein has the activity of hydrolyzing fibrinogen α chain, and this activity can be completely inhibited by metal chelators EDTA, EGTA, 1,10-phenanthroline and reducing agent DTT. | I.V | 0.3 and 3.0 mg/kg | Activity: In vitro anticoagulation platelet aggregation rate on rabbits Anticoagulant effect in rats |
2 | CN106632686 (A) | University | 2017/China | Trimeresurus fasciatus | Anti-IL-4R single-chain antibody and a snake venom L-amino acid oxidase fusion protein. | Citotoxic: Direct killing and apoptosis-inducing effects on a variety of cancer cells, selectivity lung cancer | I.P. | 100, 50, 20 mg/kg | Activity: MTT assay, effects of fusion protein on human lung adenocarcinoma cell line, effects of anti-IL-4R single-chain antibody and LAAO fusion protein on tumor inhibition rate and life extension rate of mice bearing human lung adenocarcinoma Safety: Cell line H460 |
3 | CN113388020 (A) | Research institute | 2021/China | Deinagkistrodon acutus | Peptide DAvp-1 | Anti-inflammatory: Antagonize TNF-α | I.P | 500 μg/kg | Activity: Ulcerative colitis mouse model. |
4 | CN104434981 (A) | Pharmaceutical industry | 2015/China | Naja atra | Physically treated cobra venom | Anti-inflammatory: Inhibit acute lung inflammation induced by lipopolysaccharide | Orally | 10–3000 μg/kg animal/1 to 1000 μg/kg per person. | Activity: Acute lung injury induced by LPS model |
5 | CN111617108 (A) | Pharmaceutical industry | 2020/China | Naja naja, King cobra, Bengal cobra, Bungarus, Coral snake, Black mamba | Elapheidae postsynaptic neurotoxin, cardiotoxin, cytotoxin, phospholipase A2 | Anti-viral: Membrane toxins can easily pass through the Membrane structure and then destroy internal structures such as mitochondria and lysosomes, reversibly bind to nicotinic acetylcholine receptors | NA | 1.03, 0.39, 0.23, 0.32 and 0.89 (unit: μg/mL) | Activity: Virus plaque |
6 | CN115957303 (A) | University | 2023/China | Hydrophis cyanocinctus | Polypeptide Hc-CATH | Anti-viral: Destroy the viral envelope, induce the leakage of the viral genome, and thus inactivate viral particles | I.V | 5 mg/kg | Activity: Zika in vitro/in vivo infection, Safety: Cytotoxicity assay in Vero cells |
7 | WO2023168743 (A1) | Pharmaceutical industry | 2023/WIPO | NA | Viper venom hemocoagulase (Slounase) | Procoagulant and hemostatic: Reverse the anticoagulant effect of FXa inhibitors and completely restore thrombosis in human blood. | NA | 0.014–0.077 U/mL | Activity: In vitro thromboelastography |
8 | CN108079285 (A) | Pharmaceutical industry | 2018/China | Bothrops moojeni | L-aminobutanedioic acid stabilizer for snake venom enzyme: Defibrase | Stabilizer: for making snake venom enzyme preparation safer, more effective, more stable. | NA | NA | Stability Test |
9 | US2019336572 (A1) | Research institute | 2019/United states | Naja tripudians, N. siamensis, N. naja, N. atra, N. kaouthia, and O. hannah | Cobra venom | Antinociceptive: Target the cholinergic system by blocking the activity of acetylcholine | Orally | 0.1 to about 0.5 mg/mL | Stability Test, Activity: Formalin, hot-plate and acetic acid writhing tests |
10 | KR20190102909 (A) | Pharmaceutical industry | 2019/Republic of Korea | Naja atra | Low molecular peptide isolated from the heat-treated snake venom | Anti-inflammatory: NA | NA | 50 μg/mL | Safety: Cytotoxicity |
11 | US2022362356 (A1) | Pharmaceutical industry | 2022/United states | Agkistrodon piscivorus piscivorus or Naja melanoleuca | Extract of snake venom | Anti-inflammatory: Increase the level of regulatory T cells, increased all of the level of each combination of CD4 positive, CD25 positive, can improve the inflammatory symptoms of rheumatoid arthritis. | Orally/skin application | 0.1 to 50 mg/kg | Activity: Arthritis model mice |
12 | KR20220170290 (A) | University | 2022/Republic of Korea | Republic of Korea pit viper (Gloydius brevicaudus, Gloydius intermedius, Gloydius ussuriensis) | Anti-viper serum/anti-viper viper serum | Anti-venom: venom neutralizing effect | I.M | 50 μL/100 μL) | Safety: Lethality test |
13 | US2015110770 (A1) | Research institute | 2015/United states | Crotalus durissus terrificus | Crotoxin compositions | Cytolytic: NA | I.V | 0.0012–0.01 mg/kg | Activity: Anti-tumor activity both in vitro and in vivo, Safety: LD50 |
14 | CN110724678 (A) | University | 2020/China | Agkistrodon acutus | Agkistrodon halys venom fibrinolysin- plasmin | Thrombolytic: Remove the fibrin gel blocks deposited in the thrombus on the blood vessel wall, dissolve the thrombus | Intravenous drip | 25 μg/kg, 50 μg/kg and 100 μg/kg | Activity: Determination of fibrinolytic enzyme activity, thrombolytic assay, Anticoagulant effect in mice |
15 | CN108273067 (A) | Pharmaceutical industry | 2018/China | Bothrops atrox | Glutamic acid stabilizer for snake venom enzyme: Defibrase | NA | NA | NA | Accelerated stability test |
16 | CN108743924 (A) | Pharmaceutical industry | 2018/China | NA | Snake venom coagulation factor activator | Procoagulant: clotting factor, blood coagulation X factor activator. | NA | NA | NA |
17 | CN105497873 (A) | University | 2016/China | Cobra or Agkistrodon | Light-controlled targeted snake venom polypeptide zinc nanoformulation | Antinociceptive: Central effect. | I.P | 2 mg/kg | Activity: Hot plate |
18 | CN109943554 (A) | Pharmaceutical industry | 2019/China | Vipera ruselli, Bothrops, Deinagkistrodon, Bungarus, Cerastes, Calloselasma, Ophiophagus, Crotalus adamanteus and/or Naja | Coagulation factor X activator from snake venom. | Hemostatic: Factor X activators activate factor X at the site of blood vessel damage, promoting the generation of thrombin. | NA | NA | NA |
19 | NZ753297 (A) | Pharmaceutical industry | 2021/New Zealand | Agkistrodon acutus | Recombinant Agkisacutacin | Antiplatelet: Inhibiting platelet aggregation | NA | 2 μg | Activity: GPIb binding activity and antiplatelet agglutination activity |
20 | CN109929020 (A) | Pharmaceutical industry | 2019/China | Naja, Naja atra | Neurotoxin | Antinociceptive: NA | NA | NA | NA |
21 | KR20190007161 (A) | Pharmaceutical industry | 2019/Republic of Korea | Naja atra, Naja kaouthia | Modified cobra venom | Anti-inflammatory and antinociceptive: NA | Orally, external and injectable | 300 μg/kg | Activity: Mouse Ear Swelling Assay Safety: LD50 |
22 | CN107737333 (A) | Pharmaceutical industry | 2018/China | Naja atra | 4-aminoquinoline derivative and cytotoxin-CTX1 | Anti-tumor: CTXs-mediated cancer cell damage is achieved by destroying lysosomes, induce apoptosis and necrosis of a variety of tumor cells. | NA | NA | Activity: Citotoxicity breast cancer cell line MCF7, human acute myeloid leukemia cell line KG1a |
23 | CN107929717 (A) | Pharmaceutical industry | 2018/China | Naja atra | Siramesin and snake venom cytotoxin-CTX1 | Anti-tumor: Significant synergistic effect on the growth inhibition of the MCF7 tumor line and could effectively induce late apoptosis and necrosis of MCF7 cells. | NA | NA | Activity: Citotoxicity cell line MCF7, Changes in reactive oxygen species during cell death |
24 | CN115594746 (A) | University | 2023/China | Agkistrodon acutus | C-type lectin-like protein | Anti-platelet and anti-coagulation: Effect by prolonging TT, APTT and PT pathways. | I.V | 0.5 μg/g and 1.5 μg/g | Activity: Anticoagulant effect on mice, Platelet count, Coagulation function assay, Tail bleeding time determination |
25 | CN117756907 (A) | Pharmaceutical industry | 2024/China | Naja atra | Cobra-peptide and Substance A | Antitumor: inhibits the proliferation of various cells, induce early apoptosis. | NA | NA | Activity: Human cervical cancer cell line Hela cells, Flow cytometry assay for cell apoptosis Stability test |
26 | CN107098956 (A) | University | 2017/China | Naja atra | Cytotoxin-4N | Cytotoxic: Activation or cause apoptosis | NA | NA | Activity: Effect on the inhibition of HSC-T6 cell proliferation, Effects on apoptosis of HSC-T6 cells |
27 | WO2017190263 (A1) | Pharmaceutical industry | 2017/WIPO | Naja atra | C fragment polypeptide | Antinociceptive: NA | I.M | 0.5 mg/mL | Activity: Postoperative Pain in Rats, Von Frey test |
28 | CN114409757 (A) | Pharmaceutical industry | 2022/China | Naja | Cobra venom neurotoxin | Antinociceptive: High affinity for N-type acetylcholine receptors and can block the transmission of nerve impulse signals at the neuromuscular junction | I.M | 23.3 μg/kg | Activity: Hot plate test |
29 | CN117343131 (A) | University | 2024/China | Naja atra, Gloydius brevicaudus, Deinagkistrodon, Trimeresurus stejnegeri, Bungarus multicinctus, Bungarus fasciatus, Protobothrops mucrosquamatus. | Snake venom polypeptide | Antibacterial: NA | Orally/injected | 100 mg/kg | Activity: MIC E.coli, Acute toxicity test in mice, Subacute toxicity test in mice, Hemolytic test. Safety: LD50 Stability test |
30 | CN105861476 (A) | University | 2016/China | Naja atra | PIII type metalloproteinase- Atrase A/Atrase B | Thrombolytic: Hydrolyze the α chain of fibrinogen and show anti-platelet aggregation activity | I.V | 3.0 mg/kg–0.3 mg/kg | Activity: Determination of fibrinolytic function |
31 | US2017128544 (A1) | University | 2017/United states | Naja naja, Naja kaouthia | Humanized cobra venom factor | Immunogenic: Induce a humoral or a cell mediated response of the immune system | I.P | 250 μg/kg–500 μg/kg | Activity: Murine model of age-related macular degeneration, murine model of gastrointestinal ischemia reperfusion injury. |
Application Number [Reference] | Amino Acids Sequence | Activity |
---|---|---|
CN107737333 (A) [13] | LKCNKLIPIA SKTCPAGKNL CYKMFMMSDLTIPVKRGCID VCPKNSLLVK YVCCNTDRCN | Anti-tumor |
CN115957303 (A) [13] | KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL | Anti-viral |
CN109929020 (A) [13] | LECHNQQSSQTPTTTGCSGGETNCYKKRWRDHRGYRTERGCGCPSVKNGIEINCCTTDRCNN | Analgesic |
CN117756907 (A) [13] | LECHNQQSSQ TPTTTGCSGG ETNCYKKRWRDHRGYRTERG CGCPSVKNGI EINCCTTDRC NN | Antitumor |
WO2017190263 (A1) [13] | KDHRGTRIER | Analgesic |
CN114409757 (A) [13] | LECHNQQSSQTPTTTGCSGGETNCYKKRWRDHRGYRTERGCGCPSVKDGIEINCCTTDRCNN | Analgesic |
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Zona Rubio, D.C.; Aragón, D.M.; Almeida Alves, I. Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications. Toxins 2025, 17, 136. https://doi.org/10.3390/toxins17030136
Zona Rubio DC, Aragón DM, Almeida Alves I. Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications. Toxins. 2025; 17(3):136. https://doi.org/10.3390/toxins17030136
Chicago/Turabian StyleZona Rubio, Diana Carolina, Diana Marcela Aragón, and Izabel Almeida Alves. 2025. "Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications" Toxins 17, no. 3: 136. https://doi.org/10.3390/toxins17030136
APA StyleZona Rubio, D. C., Aragón, D. M., & Almeida Alves, I. (2025). Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications. Toxins, 17(3), 136. https://doi.org/10.3390/toxins17030136