Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Raebareli, Lucknow, U.P., India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Raebareli, Lucknow, U.P., India.
Environ Sci Pollut Res Int. 2022 Feb;29(6):8759-8766. doi: 10.1007/s11356-021-16229-8. Epub 2021 Sep 7.
There are no specific drugs for the treatment of Japanese Encephalitis. Thus, new chemical entities or exploration of existing molecules is required. We have tested the antiviral potential of abscisic acid and aloe-emodin against protease of the Japanese encephalitis virus (JEV) using the computational and target-based assay. Maestro Schrödinger glide suite 2019 was used for molecular docking and dynamic studies, and NS2B-NS3A JEV protease kit was used to confirm protease inhibitory activity of abscisic acid and aloe-emodin. The abscisic acid and aloe-emodin have shown optimum binding affinity towards NS2B-NS3A protease of JEV. Furthermore, molecular dynamic simulation results have also shown the stability of abscisic acid and aloe-emodin within the binding pocket of NS2B-NS3A protease. The ADME parameters of both compounds were also found in an acceptable range. The IC50 values were found to be 100 μg/ml and 7.3 μg/ml for abscisic acid and aloe-emodin respectively which indicate more potency of aloe-emodin over the abscisic acid. However, the toxicity prediction results have shown a good safety profile of abscisic acid as compared to aloe-emodin. Thus, further, more detailed experimental studies are required to develop abscisic acid and aloe-emodin as a specific protease inhibitor of JEV.
目前尚无治疗日本脑炎的特效药物，因此需要开发新的化学实体或探索现有分子。我们使用计算和基于靶标的方法测试了脱落酸和大黄素对日本脑炎病毒（JEV）蛋白酶的抗病毒潜力。Schrödinger glide suite 2019 用于分子对接和动力学研究，使用 NS2B-NS3A JEV 蛋白酶试剂盒确认脱落酸和大黄素的蛋白酶抑制活性。脱落酸和大黄素对 JEV 的 NS2B-NS3A 蛋白酶表现出最佳的结合亲和力。此外，分子动力学模拟结果还表明，脱落酸和大黄素在 NS2B-NS3A 蛋白酶结合口袋内具有稳定性。两种化合物的 ADME 参数也在可接受范围内。脱落酸和大黄素的 IC50 值分别为 100 μg/ml 和 7.3 μg/ml，表明大黄素比脱落酸更有效。然而，毒性预测结果表明，与大黄素相比，脱落酸具有更好的安全性。因此，需要进一步开展更详细的实验研究，以开发脱落酸和大黄素作为 JEV 的特异性蛋白酶抑制剂。
