Kumar Mala S, R Amjesh, Bhaskaran Silpa, D Delphin R, Nair Achuthsankar S, R Sudhakaran P
Department of Computational Biology and Bioinformatics, Karyavattom, University of Kerala, Thiruvananthapuram, Kerala, 695581, India.
J Mol Model. 2019 Mar 8;25(4):88. doi: 10.1007/s00894-019-3954-2.
Alternative treatments from plant-derived small molecules for neutralizing the venom lethality in snake envenomation are prevalent now. Elephantopus scaber, a tropical plant species has been recognized for its various pharmacological activities and especially anti-snake venom property; however, the molecular basis for this property is not understood. It is reported that snake venom PLA2 is a toxic factor with pharmacological effects independent of their catalytic activity. Here we report the inhibition of catalytic property of Cobra and Viper (group I and group II) snake venom PLA2 by the phytocompounds from E. scaber through molecular docking and dynamics studies. Initially, Lipinski's rule, ADMET, and molecular docking studies were carried out. Our results show that among 124 phytocompounds, crepiside E (deacylcynaropicrin-3' beta-glucopyranoside) has shown interactions with the conserved catalytic active site residues, His 48 and Asp 49, in both the PLA2s. Further, molecular dynamic simulations for 60 ns confirmed the stability of crepiside E in the active site of PLA2s and were found to be stable throughout the simulation. In order to understand the drug-likeness of crepiside E, pIC50 and MMGBSA scores were correlated by performing a linear regression analysis. Crepiside E was found to have similar chemical features to that of doxycycline, a known PLA2 inhibitor as indicated by a similarity score of 64.15%. Hence, it is concluded that crepiside E beta glucopyranoside present in Elephantopus scaber contributes to neutralizing the snake venom.
目前，源自植物的小分子用于中和蛇咬伤中毒液致死性的替代疗法很普遍。地胆草，一种热带植物，因其多种药理活性，尤其是抗蛇毒特性而闻名；然而，这种特性的分子基础尚不清楚。据报道，蛇毒PLA2是一种具有药理作用的毒性因子，其药理作用与其催化活性无关。在此，我们通过分子对接和动力学研究报告了地胆草中的植物化合物对眼镜蛇和蝰蛇（I组和II组）蛇毒PLA2催化特性的抑制作用。最初，进行了Lipinski规则、ADMET和分子对接研究。我们的结果表明，在124种植物化合物中，还阳参苷E（去酰基菜蓟苦素-3'β-葡萄糖苷）与两种PLA2中保守的催化活性位点残基His 48和Asp 49都有相互作用。此外，60纳秒的分子动力学模拟证实了还阳参苷E在PLA2活性位点的稳定性，并且在整个模拟过程中都保持稳定。为了了解还阳参苷E的类药性，通过进行线性回归分析将pIC50和MMGBSA分数进行了关联。结果发现，还阳参苷E与已知的PLA2抑制剂强力霉素具有相似的化学特征，相似性分数为64.15%。因此，得出结论，地胆草中存在的还阳参苷Eβ-葡萄糖苷有助于中和蛇毒。
