Abstract

Hemiscorpius lepturus (H. lepturus) which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against H. lepturus for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues—His12 and His48—into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD100 of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by H. lepturus in future clinical studies.

Highlights

  • The envenomation by H. lepturus is one of the greatest problems from a clinical viewpoint in the southwestern area of Iran, especially in Khuzestan Province [1]

  • I-TASSER server’s calculations, of the 292 rPLD1-amino acid residues, 114 of them are in the α-helix, 49 of them in the β-sheet and 129 in the random coil configurations

  • As for the mut-rPLD1, 112 residues are in the α-helix, 48 in the β-sheet and 132 in the random coil configurations, which in turn make up 38.35%, 16.43% and 45.22% respectively of the mut-rPLD1 structure (Figure 1)

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Summary

Introduction

The envenomation by H. lepturus is one of the greatest problems from a clinical viewpoint in the southwestern area of Iran, especially in Khuzestan Province [1]. This phenomenon has been recurrently reported in Iran [2]. H. lepturus is only responsible for about 15% of scorpion stings throughout Iran, but due to the nature of its venom it accounts for about 95% of all mortalities caused by scorpion stings [6]. According to the painless nature of its venom and slow development of symptoms in the victims, the stung patients

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