Programme in Bioinformatics and Computational Biology, Graduate school, Chulalongkorn University, Bangkok, 10330, Thailand.
Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
Sci Rep. 2023 Jun 30;13(1):10652. doi: 10.1038/s41598-023-36742-9.
The Thai banded tiger wasp (Vespa affinis) is a dangerous vespid species found in Southeast Asia, and its stings often result in fatalities due to the presence of lethal phospholipase A[Formula: see text], known as Vespapase or Ves a 1. Developing anti-venoms for Ves a 1 using chemical drugs, such as chemical drug guide, remains a challenging task. In this study, we screened 2056 drugs against the opening conformation of the venom using the ZINC 15 and e-Drug 3D databases. The binding free energy of the top five drug candidates complexed with Ves a 1 was calculated using 300-ns-MD trajectories. Our results revealed that voxilaprevir had a higher binding free energy at the catalytic sites than other drug candidates. Furthermore, the MD simulation results indicated that voxilaprevir formed stable conformations within the catalytic pocket. Consequently, voxilaprevir could act as a potent inhibitor, opening up avenues for the development of more effective anti-venom therapeutics for Ves a 1.
泰国带纹虎头蜂(Vespa affinis)是一种在东南亚发现的危险胡蜂物种,其蛰刺常常会因致命的磷脂酶 A[公式:见正文]的存在而导致死亡,这种酶被称为 Vespa 酶或 Ves a 1。使用化学药物(如化学药物指南)来开发针对 Ves a 1 的抗毒液仍然是一项具有挑战性的任务。在这项研究中,我们使用 ZINC 15 和 e-Drug 3D 数据库筛选了 2056 种针对毒液开放构象的药物。使用 300-ns-MD 轨迹计算了与 Ves a 1 结合的前五名候选药物的结合自由能。我们的研究结果表明, voxilaprevir 在催化部位与 Ves a 1 的结合自由能高于其他候选药物。此外,MD 模拟结果表明,voxilaprevir 在催化口袋内形成了稳定的构象。因此,voxilaprevir 可以作为一种有效的抑制剂,为开发针对 Ves a 1 的更有效的抗毒液治疗方法开辟了道路。