Rajendran Barani Kumar, Xavier Suresh M, Bhaskaran Shanmuga Priya, Harshitha Yarradoddi, Gaur Uma, Kwok Hang Fai
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau.
Department of Physics, Sathyabama Institute of Science and Technology, Deemed to be University, Chennai 600119, India.
Comput Struct Biotechnol J. 2018 Oct 31;16:450-461. doi: 10.1016/j.csbj.2018.10.005. eCollection 2018.
Venomous reptiles especially serpents are well known for their adverse effects after accidental conflicts with humans. Upon biting humans these serpents transmit arrays of detrimental toxins with diverse physiological activities that may either lead to minor symptoms such as dermatitis and allergic response or highly severe symptoms such as blood coagulation, disseminated intravascular coagulation, tissue injury, and hemorrhage. Other complications like respiratory arrest and necrosis may also occur. Bungarotoxins are a group of closely related neurotoxic proteins derived from the venom of kraits () one of the six most poisonous snakes in India whose bite causes respiratory paralysis and mortality without showing any local symptoms. In the current study, by employing various pharmacoinformatic approaches, we have explored the antidote properties of 849 bioactive phytochemicals from 82 medicinal plants which have already shown antidote properties against various venomous toxins. These herbal compounds were taken and pharmacoinformatic approaches such as ADMET, docking and molecular dynamics were employed. The three-dimensional modelling approach provides structural insights on the interaction between bungarotoxin and phytochemicals. simulations proved to be an effective analytical tools to investigate the toxin-ligand interaction, correlating with the affinity of binding. By analyzing the results from the present study, we proposed nine bioactive phytochemical compounds which are, 2-dodecanol, 7-hydroxycadalene, indole-3-(4'-oxo)butyric acid, nerolidol-2, trans-nerolidol, eugenol, benzene propanoic acid, 2-methyl-1-undecanol, germacren-4-ol can be used as antidotes for bungarotoxin.
有毒爬行动物，尤其是蛇类，因其与人类意外冲突后产生的不良影响而广为人知。这些蛇类咬人时会传播一系列具有不同生理活性的有害毒素，这些毒素可能导致轻微症状，如皮炎和过敏反应，或严重症状，如血液凝固、弥散性血管内凝血、组织损伤和出血。其他并发症如呼吸骤停和坏死也可能发生。银环蛇毒素是一组密切相关的神经毒性蛋白质，源自印度六种最毒的蛇之一——金环蛇的毒液，其咬伤会导致呼吸麻痹和死亡，且无任何局部症状。在当前的研究中，我们采用了各种药物信息学方法，探索了82种药用植物中849种具有生物活性的植物化学物质的解毒特性，这些植物化学物质已显示出对各种有毒毒素的解毒特性。我们采用了这些草药化合物，并运用了ADMET、对接和分子动力学等药物信息学方法。三维建模方法提供了关于银环蛇毒素与植物化学物质相互作用的结构见解。分子动力学模拟被证明是研究毒素-配体相互作用的有效分析工具，与结合亲和力相关。通过分析本研究的结果，我们提出了九种具有生物活性的植物化学化合物，即2-十二醇、7-羟基杜松烯、吲哚-3-(4'-氧代)丁酸、橙花叔醇-2、反式橙花叔醇、丁香酚、苯丙酸、2-甲基-1-十一醇、吉马烯-4-醇，可作为银环蛇毒素的解毒剂。
