治疗新冠中药中的小RNA可靶向新冠患者的差异基因

Herbal small RNAs in patients with COVID-19 linked to reduced DEG expression

在中国, 80%以上的2019冠状病毒病(coronavirus disease 2019, COVID-19)患者接受了传统中药(traditional Chinese medicine, TCM)治疗,其临床疗效已有报道.然而,中药治疗新冠病毒病的潜在分子机制仍不清楚.此前研究发现,中药小RNA(small RNA, sRNA)是中药新的有效成分.本研究对22名采用透解祛瘟颗粒进行治疗的新冠病毒病患者进行了队列分析.观察到服用透解祛瘟颗粒后,数千种草药小RNA进入了患者血细胞中.与此相应,患者体内下调的新冠差异表达基因与血液中检测到的高丰度中药小RNA的预测靶基因高度相关.此外,本研究计算了本草数据库中245种中药饮片所含有的丰度最高的前30条小RNA的预测靶基因占新冠病毒病患者的337个上调差异表达基因的比例,其中33种中药饮片的预测靶点所占比例超过了50%,这些中药饮片被认为是治疗COVID-19潜在的有效饮片.其中,来自橘红、瓜蒌皮与佛手的丰度最高的前30条小RNA的预测靶基因被实验证实.本研究不仅阐明了中药对新冠病毒病患者临床疗效的新的分子机制,也为新冠治疗处方的优化提供了科学依据.

In China, more than 80% of patients with coronavirus disease 2019 (COVID-19) received traditional Chinese medicine (TCM) as atreatment and their clinical efficacy have been reported. However, the underlying molecular mechanism remains unclear. Previousstudies have identified herbal small RNAs (sRNAs) as novel functional components. In this study, a cohort of 22 patients withCOVID-19 treated with Toujie Quwen (TQ) granules was analyzed. We observed thousands of herbal small RNAs that entered theblood cells of patients after the consumption of TQ granules. In response to this treatment, the reduced differentially expressed genes(DEGs) were highly correlated with the predicted target genes of the most prevalent herbal sRNAs detected in the blood. Moreover,the predicted target genes of the top 30 sRNAs from each of the 245 TCMs in the Bencao sRNA Atlas overlapped with 337upregulated DEGs in patients with mild COVID-19, and 33 TCMs, with more than 50% overlapping genes were identified aseffective TCMs. These predicted target genes of top 30 sRNAs from Juhong, Gualoupi and Foshou were confirmed experimentally.Our results not only elucidated a novel molecular mechanism of TCM potential clinical efficacy for COVID-19 patients, but alsoprovided 33 effective COVID-19 TCMs for prescription optimization.