Induced intra- and intermolecular template switching as a therapeutic mechanism against RNA viruses

RNAseq experiments of Enterovirus A71 wild type demonstrate that the pyrazine-carboxamide ribonucleotide stimulates catalyzed intra- and intermolecular template switching. These results suggest that pyrazine-2 carboxamide ribonucleotides do not induce lethal mutagenesis or chain termination, but function by promoting template switching and formation of defective viral genomes. We conclude that RdRp-catalyzed intra- and intermolecular template switching can be induced by pyrazine-carboxamide ribonucleotides, defining an additional mechanistic class of antiviral ribonucleotides with potential for broad-spectrum activity. mRNA profiles of Enterovirus A71-inefected RD cells, in presence of different T-1106 concentrations

针对野生型肠道病毒A71（Enterovirus A71）的RNA测序（RNA sequencing, RNAseq）实验显示，吡嗪甲酰胺核糖核苷酸（pyrazine-carboxamide ribonucleotide）可促进RNA依赖的RNA聚合酶（RNA-dependent RNA polymerase, RdRp）催化的分子内与分子间模板切换。
上述结果表明，吡嗪-2-甲酰胺核糖核苷酸不会诱导致死性诱变或链终止，而是通过促进模板切换与缺陷型病毒基因组的形成发挥作用。
本研究得出结论：吡嗪甲酰胺核糖核苷酸可诱导RdRp催化的分子内与分子间模板切换，这界定了一类具备广谱抗病毒活性潜力的新型抗病毒核糖核苷酸作用机制。
本数据集涵盖不同T-1106浓度处理下，肠道病毒A71感染的RD细胞的mRNA表达谱。