Molecular docking revealed the binding of nucleotide/side inhibitors to Zika viral polymerase solved structures

A new Zika virus (ZIKV) outbreak started in 2015. According to the World Health Organization, 84 countries confirmed ZIKV infection. RNA-dependent RNA polymerase (RdRp) was an appealing target for drug designers during the last two decades. Through molecular docking, we screened 16 nucleotide/side inhibitors against ZIKV RdRp. While the mode of interaction with ZIKV is different from that in the hepatitis C virus (HCV), nucleotide/side inhibitors in this study (mostly anti-HCV) showed promising binding affinities (−6.2 to −9.7 kcal/mol calculated by AutoDock Vina) to ZIKV RdRp. Setrobuvir, YAK and, to a lesser extent, IDX-184 reveal promising results compared to other inhibitors in terms of binding ZIKV RdRp. These candidates would be powerful anti-ZIKV drugs.

2015年，新型寨卡病毒（Zika virus, ZIKV）疫情暴发。据世界卫生组织统计，全球已有84个国家确认存在寨卡病毒感染病例。近二十年来，RNA依赖型RNA聚合酶（RNA-dependent RNA polymerase, RdRp）一直是药物研发领域极具吸引力的药物靶点。本研究通过分子对接技术，针对寨卡病毒RdRp筛选了16种核苷酸/侧链抑制剂。尽管此类抑制剂与寨卡病毒的相互作用模式与丙型肝炎病毒（hepatitis C virus, HCV）中的结合模式存在差异，但本研究中的核苷酸/侧链抑制剂（多数为抗丙型肝炎病毒抑制剂）对寨卡病毒RdRp展现出良好的结合活性，其经AutoDock Vina计算得到的结合能介于-6.2至-9.7 kcal/mol之间。与其他抑制剂相比，塞托韦（Setrobuvir）、YAK以及效果稍弱的IDX-184在结合寨卡病毒RdRp方面表现出更优异的潜力。上述候选化合物有望成为高效的抗寨卡病毒药物。