Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Kolkata, India.
Discipline of Natural Sciences, Indian Institute of Information Technology, Design and Manufacturing, Jabalpur, India.
J Biomol Struct Dyn. 2024;42(19):10101-10113. doi: 10.1080/07391102.2023.2255648. Epub 2023 Sep 25.
To date, no approved drugs are available to treat the Zika virus (ZIKV) infection. Therefore, it is necessary to urgently identify potential drugs against the ZIKV infection. Here, the repurposing of 30 antiparasitic drugs against the NS2B-NS3 protease of the ZIKV has been carried out by using combined docking and molecular dynamics- (MD) simulations. Based on the docking results, 5 drugs, such as Amodiaquine, Primaquine, Paromomycin, Dichlorophene, and Ivermectin were screened for further analysis by MD simulations and free energy calculations. Among these drugs, Amodiaquine and Dichlorophen are found to produce the most stable complexes and possess relative binding free energies of about -44.3 ± 3.7 kcal/mol and -41.1 ± 5.3 kcal/mol respectively. Therefore, they would act as potent small-molecule inhibitors of the ZIKV protease.However, evaluations of biological and safety activities of these drugs against the ZIKV protease are required before their clinical use.Communicated by Ramaswamy H. Sarma.
迄今为止，尚无获准用于治疗寨卡病毒（ZIKV）感染的药物。因此，有必要紧急寻找针对 ZIKV 感染的潜在药物。在这里，通过联合对接和分子动力学-（MD）模拟，对 30 种抗寄生虫药物进行了针对 ZIKV 的 NS2B-NS3 蛋白酶的再利用。根据对接结果，通过 MD 模拟和自由能计算筛选出 5 种药物，如阿莫地喹、伯氨喹、巴龙霉素、双氯芬酸和伊维菌素进行进一步分析。在这些药物中，发现阿莫地喹和双氯芬酸产生最稳定的复合物，并且具有约-44.3±3.7 kcal/mol 和-41.1±5.3 kcal/mol 的相对结合自由能。因此，它们将作为 ZIKV 蛋白酶的有效小分子抑制剂。然而，在这些药物用于临床之前，需要对它们针对 ZIKV 蛋白酶的生物学和安全性进行评估。Ramaswamy H. Sarma 通讯。
