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The chemistry of snake venom and its medicinal potential

Nature Reviews Chemistry volume 6, pages 451–469 (2022)Cite this article

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Abstract

The fascination and fear of snakes dates back to time immemorial, with the first scientific treatise on snakebite envenoming, the Brooklyn Medical Papyrus, dating from ancient Egypt. Owing to their lethality, snakes have often been associated with images of perfidy, treachery and death. However, snakes did not always have such negative connotations. The curative capacity of venom has been known since antiquity, also making the snake a symbol of pharmacy and medicine. Today, there is renewed interest in pursuing snake-venom-based therapies. This Review focuses on the chemistry of snake venom and the potential for venom to be exploited for medicinal purposes in the development of drugs. The mixture of toxins that constitute snake venom is examined, focusing on the molecular structure, chemical reactivity and target recognition of the most bioactive toxins, from which bioactive drugs might be developed. The design and working mechanisms of snake-venom-derived drugs are illustrated, and the strategies by which toxins are transformed into therapeutics are analysed. Finally, the challenges in realizing the immense curative potential of snake venom are discussed, and chemical strategies by which a plethora of new drugs could be derived from snake venom are proposed.

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Fig. 1: Composition of the venom of snakes from the Elapidae and Viperidae families.
Fig. 2: The three main types of PLA2 bound to their targets.
Fig. 3: Structures of SVMPs and their substrates.
Fig. 4: Structure of SVSPs and their substrates.
Fig. 5: Approved drugs derived from snake venoms.
Fig. 6: Drugs derived from snake venoms in clinical or preclinical trials.

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Acknowledgements

The authors acknowledge financial support from FCT/MCTES — the Portuguese Foundation for Science and Technology — through project PTDC/QUI-OUT/1401/2020 and from the Associate Laboratory for Green Chemistry (LAQV), which is financed by FCT/MCTES within the scope of project UIDB/50006/2020. M.F.V. acknowledges FCT/MCTES for PhD grant SFRH/BD/119206/2016. The authors thank the technological platforms network of the Oswaldo Cruz Foundation (FIOCRUZ) for the support and financing of the services provided by the Flow Cytometry and the Bioprospection and Molecular Interaction facilities/FIOCRUZ Rondônia and o Programa de Excelência em Pesquisa (PROEP) da FIOCRUZ Rondônia. The authors also thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Rondônia (FAPERO) and Instituto Nacional de Ciência e Tecnologia em Epidemiologia da Amazônia Ocidental (INCT-EpiAmO) from Brazil for financial support.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal

    Ana L. Oliveira, Matilde F. Viegas, Saulo L. da Silva, Maria J. Ramos & Pedro A. Fernandes

  2. LAQV/Requimte, University of Porto, Porto, Portugal

    Ana L. Oliveira, Matilde F. Viegas, Saulo L. da Silva, Maria J. Ramos & Pedro A. Fernandes

  3. Biotechnology Laboratory for Proteins and Bioactive Compounds from the Western Amazon, Oswaldo Cruz Foundation, National Institute of Epidemiology in the Western Amazon (INCT-EpiAmO), Porto Velho, Brazil

    Andreimar M. Soares

  4. Sao Lucas Universitary Center (UniSL), Porto Velho, Brazil

    Andreimar M. Soares

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  1. Ana L. Oliveira
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  2. Matilde F. Viegas
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Contributions

All authors contributed to the discussion of content and edited the article prior to submission. P.A.F., A.L.O., M.F.V. and M.J.R. also researched the data and contributed to the writing of the article.

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Correspondence to Pedro A. Fernandes.

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Nature Reviews Chemistry thanks Juan J. Calvete and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

The Reptile Database: http://www.reptile-database.org/

Supplementary information

Glossary

Neurotoxicity

The ability of a substance to negatively affect the structure or function of the central or peripheral nervous system.

Haemotoxicity

The ability of a substance to negatively affect the cardiovascular system or disrupt haemostasis.

Cytotoxicity

The ability of a substance to negatively affect the structure or function of cells.

Toxins

Toxic compounds produced by a living organism or a virus.

Elapidae

Family of >300 venomous snakes with fixed front fangs. Their venom is often neurotoxic. This family includes the mambas, cobras, coral snakes and most Australian snakes, among others.

Viperidae

Family of >300 venomous heavy-body snakes with long, retractable front fangs. Their venom is frequently haemotoxic and cytotoxic. This family includes Old World vipers, rattlesnakes and lanceheads, among others.

Medically important snakes

Snake species that cause notable morbidity and mortality. This classification depends on the venom toxicity, the frequency of snake–human interactions, the aggressiveness of the snake and the health-care facilities.

Myotoxicity

Cytotoxicity specifically directed to myocytes (muscle cells).

C-type lectins

Superfamily of >1,000 proteins, most of which bind carbohydrates in a Ca2+-dependent manner. The proteins share a C-type lectin-like domain in their carbohydrate-binding region. In snake venoms, they are haemotoxic.

C-type lectin-like proteins

A protein family whose members feature a domain with the C-type lectin fold, which lacks critical structural elements to recognize and bind sugars. In snake venoms, these proteins are haemotoxic.

Sarcolemma

Specialized type of cell plasma membrane that surrounds muscle cells. It is frequently the target of snake venom myotoxins.

Lysosomes

Membrane-bound organelle containing digestive, hydrolytic enzymes whose function is primarily the degradation of macromolecules, old cell parts and microorganisms. Lysosomes represent the waste disposal of a cell.

Neuromuscular junction

A specialized synapse established between a motor neuron and a muscle fibre through which signals for muscle contraction are transmitted.

Fibrinogen

A protein complex in the plasma of vertebrates that is enzymatically and sequentially converted into fibrin and a fibrin-based blood clot. Fibrinogen is responsible for stopping bleeding from blood vessels.

Intrathecal administration

Invasive drug administration by injection through the skull or the spine, allowing the drug to reach the cerebrospinal fluid, and thus the brain, without crossing the blood–brain barrier.

Natriuresis

The process of excretion of sodium in the urine.

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Oliveira, A.L., Viegas, M.F., da Silva, S.L. et al. The chemistry of snake venom and its medicinal potential. Nat Rev Chem 6, 451–469 (2022). https://doi.org/10.1038/s41570-022-00393-7

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