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

In China, more than 80% of patients with coronavirus disease 2019 (COVID-19) received traditional Chinese medicine (TCM) as a treatment and their clinical efficacy have been reported. However, the underlying molecular mechanism remains unclear. Previous studies have identified herbal small RNAs (sRNAs) as novel functional components. In this study, a cohort of 22 patients with COVID-19 treated with Toujie Quwen (TQ) granules was analyzed. We observed thousands of herbal small RNAs that entered the blood 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 337 upregulated DEGs in patients with mild COVID-19, and 33 TCMs, with more than 50% overlapping genes were identified as effective 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 also provided 33 effective COVID-19 TCMs for prescription optimization.