Rational design of selective inhibitors targeting snake venom based on resistance system of venomous snake

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Fukuoka University
• Principal Investigator: Aoki-Shioi Narumi (青木成留実) 福岡大学, 理学部, 助教 (50510187)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 蛇毒液 / 阻害剤 / 毒ヘビ / 蛇毒咬傷

Outline of Final Research Achievements

A significant achievement was the acquisition of high-quality data from transcriptome analysis of the venom glands (or salivary glands) as well as various tissues of the Japanese vipers, elapid, and non-venomous snake. In addition, we successfully determined the crystal structure of synergistic-type toxin that significantly enhance the toxicity of snake venom toxin. Finally, we focused on several candidate genes and proteins specific expressed in venomous snakes by comparative analysis between venomous and non-venomous snakes based on transcriptome and proteomics analysis, which would provide insight into potential mechanisms a system for production of toxins. We also identified serum proteins that specifically bind to three-finger toxins with existing in elapid as the lethal toxin. As we have succeeded in establishing methods for preparing toxins and their binding proteins, we are currently conducting crystallization for structural analysis.

Free Research Field

毒素科学

Academic Significance and Societal Importance of the Research Achievements

WHOはヘビ咬傷被害は年間約2.7百万人、死者14万人という実態を明らかにし、世界的な支援を求めている。ヘビ咬傷治療は、ヘビ毒液を免疫したウマの抗血清投与である。しかし、その治療はアナフィラキシーショックなど致死的副作用および抗血清の価格が高すぎるなどの問題点がある。本研究では代表者が見出したヘビ毒阻害タンパク質を基盤にヒトに対して安全でかつ安価な治療法の提案を目指しており、毒素に対して高い特異性と安定性を持つ阻害物質の創薬基盤研究である。構造学的分子メカニズムの解明は、具体的な創薬デザインを可能とするだけでなく、毒ヘビに関する研究や医学、生物学の分野において重要な貢献となることが期待される。