Fearns Rachel, Plemper Richard K
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, United States.
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, United States.
Virus Res. 2017 Apr 15;234:87-102. doi: 10.1016/j.virusres.2017.01.008. Epub 2017 Jan 16.
The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these viruses are multi-functional complexes, capable of transcribing subgenomic capped and polyadenylated mRNAs and replicating the genome. Although there is no native structure available for any complete paramyxo- or pneumovirus polymerase, functional and structural studies of a fragment of a pneumovirus polymerase protein and mutation analyses and resistance profiling of small-molecule inhibitors have generated a wealth of mechanistic information. This review integrates these data with the structure of a related polymerase, identifying similarities, differences, gaps in knowledge, and avenues for antiviral drug development.
副粘病毒和肺病毒属于单股负链RNA病毒目,这是一类具有非节段性负链RNA基因组的病毒。这些病毒的聚合酶是多功能复合物,能够转录亚基因组加帽和聚腺苷酸化的mRNA并复制基因组。尽管目前尚无完整的副粘病毒或肺病毒聚合酶的天然结构,但对肺病毒聚合酶蛋白片段的功能和结构研究以及小分子抑制剂的突变分析和耐药性分析已经产生了大量的机制信息。本综述将这些数据与相关聚合酶的结构相结合,确定了相似性、差异、知识空白以及抗病毒药物开发的途径。