Singh Anjali, Jana Nandan Kumar
Department of Biotechnology, Heritage Institute of Technology, Kolkata 700107, India.
Comput Biol Chem. 2017 Dec;71:144-151. doi: 10.1016/j.compbiolchem.2017.10.007. Epub 2017 Oct 24.
Zika virus (ZIKV) infection has been associated with Guillain-Barre syndrome in adults and microcephaly in infants. The existence of insufficient structural data in most of the protein databases hinders the synthesis of anti-ZIKV pharmaceutics. In this work, we attempted to model the catalytic domain of the ZIKV RNA polymerase (RdRpC) along with a detailed assessment of conserved aspartates in ZIKV RdRpC palm domain as potential drug targets. The conserved and catalytically active aspartate residues present in the predicted RdRpC protein were virtually screened against a ZINC database for inhibitors, and the selected potential drug candidates were further filtered based on their ADMET profiles. One of the pharmacokinetically active compounds (Ligand 6) showed a remarkable docking profile against the strictly conserved aspartate residues of the RdRpC active site. We hypothesize that the Ligand 6 may form a potential drug candidate for RdRpC inhibition in the clinical treatment of ZIKV infection.
寨卡病毒（ZIKV）感染与成人的吉兰-巴雷综合征以及婴儿的小头畸形有关。大多数蛋白质数据库中结构数据不足，这阻碍了抗寨卡病毒药物的合成。在这项工作中，我们试图对寨卡病毒RNA聚合酶的催化结构域（RdRpC）进行建模，并详细评估寨卡病毒RdRpC手掌结构域中保守的天冬氨酸作为潜在药物靶点。针对预测的RdRpC蛋白中存在的保守且具有催化活性的天冬氨酸残基，在ZINC数据库中虚拟筛选抑制剂，然后根据所选潜在药物候选物的药代动力学性质进一步筛选。其中一种具有药代动力学活性的化合物（配体6）对RdRpC活性位点严格保守的天冬氨酸残基显示出显著的对接情况。我们推测，配体6可能成为临床治疗寨卡病毒感染时抑制RdRpC的潜在药物候选物。
