Antigenic and Substrate Preference Differences between Scorpion and Spider Dermonecrotic Toxins, a Comparative...

Area of Science:

• Biochemistry
• Toxicology
• Molecular Biology

Background:

• The scorpion *Hemiscorpius lepturus* and the brown spider *Loxosceles intermedia* are significant public health concerns in Asia and America, respectively.
• Their venoms contain distinct yet similar toxins, primarily phospholipase D enzymes, responsible for envenomation's clinical effects.

Purpose of the Study:

• To compare the enzymatic properties of recombinant Heminecrolysin (rHNC) from *H. lepturus* and rLiD1 from *L. intermedia*.
• To investigate potential cross-reactivity and epitopic similarities between these major venom phospholipase D toxins.

Main Methods:

• Competitive ELISA and hemolytic inhibition assays were employed to assess venom cross-reactivity and antibody interactions.
• Enzymatic assays, including cellular and in-silico analyses of hydrogen bonds, were used to determine substrate specificity and reaction products.

Main Results:

• A cross-reaction was observed between scorpion and spider venoms, indicating epitopic similarity between rHNC and rLiD1.
• rHNC and rLiD1 demonstrated equivalent hydrolysis of lysophosphatidylcholine (LPC) and sphingomyelin, respectively.
• rHNC exclusively catalyzed transphosphatidylation of LPC to produce cyclic phosphatidic acid (cPA).
• Lysophosphatidic acid (LPA) was identified as a novel substrate for both rHNC and rLiD1.

Conclusions:

• The study reveals shared antigenic epitopes and functional similarities between rHNC and rLiD1.
• The identification of LPA as a substrate and cPA as a product provides novel molecular insights into the pathogenesis of *H. lepturus* envenomation and loxoscelism.