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

Gutiérrez, José María; Albulescu, Laura-Oana; Clare, Rachel H.; Casewell, Nicholas R.; Abd El-Aziz, Tarek Mohamed; Escalante, Teresa; Rucavado, Alexandra

doi:10.3390/toxins13070451

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

^1,*

²,

²,

Tarek Mohamed Abd El-Aziz

^3,4

Teresa Escalante

¹ and

Alexandra Rucavado

Facultad de Microbiología, Instituto Clodomiro Picado, Universidad de Costa Rica, San José 11501, Costa Rica

Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK

Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt

⁴

Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA

Author to whom correspondence should be addressed.

Toxins 2021, 13(7), 451; https://doi.org/10.3390/toxins13070451

Received: 30 May 2021 / Revised: 23 June 2021 / Accepted: 27 June 2021 / Published: 29 June 2021

(This article belongs to the Special Issue Animal Poisons and Venoms in Drug Discovery)

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Abstract

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

Keywords: snake venom; antivenom; inhibitors; metalloproteinases; phospholipases A₂; three finger toxins; peptidomimetic hydroxamates; varespladib

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MDPI and ACS Style

Gutiérrez, J.M.; Albulescu, L.-O.; Clare, R.H.; Casewell, N.R.; Abd El-Aziz, T.M.; Escalante, T.; Rucavado, A. The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming. Toxins 2021, 13, 451. https://doi.org/10.3390/toxins13070451

AMA Style

Gutiérrez JM, Albulescu L-O, Clare RH, Casewell NR, Abd El-Aziz TM, Escalante T, Rucavado A. The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming. Toxins. 2021; 13(7):451. https://doi.org/10.3390/toxins13070451

Chicago/Turabian Style

Gutiérrez, José M., Laura-Oana Albulescu, Rachel H. Clare, Nicholas R. Casewell, Tarek M. Abd El-Aziz, Teresa Escalante, and Alexandra Rucavado. 2021. "The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming" Toxins 13, no. 7: 451. https://doi.org/10.3390/toxins13070451

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