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Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors

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Abstract

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A2 (SvPLA2) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA2 catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA2 toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A2, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA2, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA2 effect.

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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

cPLA2 :

Cytosolic PLA2

GI, GII:

Group I and Group II

LAAO:

L-amino acid oxidase

PLA2 :

Phospholipase A2

sPLA2 :

Secretory phospholipase A2

SvPLA2 :

Snake venom phospholipase A2

VEGFR-2:

Vascular endothelial growth factor receptor-2

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Funding

This research is funded by the ICMR-National Institute of Traditional Medicine, Belagavi, India.

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Authors and Affiliations

  1. ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, 590010, India

    Ganesh H. Sampat, Kashinath Hiremath, Jagadeesh Dodakallanavar, Vishal S. Patil, Darasaguppe R. Harish, Manish Barvaliya & Subarna Roy

  2. KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, 590010, India

    Ganesh H. Sampat, Kashinath Hiremath, Jagadeesh Dodakallanavar, Vishal S. Patil & Prakash Biradar

  3. Department of Animal Nutrition, Veterinary College, Bangalore, Karnataka, 560024, India

    Rashmi K. Mahadevamurthy

Authors
  1. Ganesh H. Sampat
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  9. Subarna Roy
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Contributions

GHS: Main worker, designing of work, writing the original draft. KH: Data curation and review. JD: Data curation and review. VSP: Review and drafting. DRH: Supervision, concept, data curation, and review. PB: Co-Supervision. RKM: Review. MB: Review. SR: Co-supervision and review.

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Correspondence to Darasaguppe R. Harish or Prakash Biradar.

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Sampat, G.H., Hiremath, K., Dodakallanavar, J. et al. Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors. Pharmacol. Rep 75, 1454–1473 (2023). https://doi.org/10.1007/s43440-023-00543-8

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