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

Abstract

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. Supporting Information The supporting information is available online at 10.1007/s11427-022-2225-3. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Nanoparticles derived from herbal preparations May represent a novel nucleic acid therapy

“…8,9,14 Previous studies have demonstrated favorable biocompatibility and effectiveness, establishing them as innovative methods for delivering nucleic acids orally. [14][15][16]32,33,35 However, the field is FENG ET AL.…”

“…30 In response, Jiang's group reported the similarity/shared characteristics between plant and animal non-coding sRNA, revealing some shared RNA sequences, suggesting possible cross-kingdom sharing between plant and animal genomes. [31][32][33] It's worth mentioning that traditional Chinese medicine is effective in treating patients with COVID-19 in China, but the specific mechanism is complex and challenging to clarify. 34 Interestingly, Jiang's group first reported that in the peripheral blood mononuclear cells (PBMCs) samples of COVID-19 patients treated with traditional Chinese medicine, many sRNAs derived from herbal sources were identified.…”

“…The predicted target genes of these sRNAs showed approximately 80% overlap with the differentially expressed genes (DEGs) in COVID-19 patients, suggesting a potential interplay between sRNAs and the regulation of DEGs during treatment. 33 However, because the disease progression itself might influence DEGs, the underlying molecular mechanisms still need validation and clarification.…”

“…In response to Professor Jiang's group's findings, Lu argued that the highly conserved animal miRNA sequences found in plant sRNA indicate a non‐plant origin, which infers that animal sRNA contamination in decoctions 30 . In response, Jiang's group reported the similarity/shared characteristics between plant and animal non‐coding sRNA, revealing some shared RNA sequences, suggesting possible cross‐kingdom sharing between plant and animal genomes 31–33 . It's worth mentioning that traditional Chinese medicine is effective in treating patients with COVID‐19 in China, but the specific mechanism is complex and challenging to clarify 34 .…”

“…Interestingly, Jiang's group first reported that in the peripheral blood mononuclear cells (PBMCs) samples of COVID‐19 patients treated with traditional Chinese medicine, many sRNAs derived from herbal sources were identified. The predicted target genes of these sRNAs showed approximately 80% overlap with the differentially expressed genes (DEGs) in COVID‐19 patients, suggesting a potential interplay between sRNAs and the regulation of DEGs during treatment 33 . However, because the disease progression itself might influence DEGs, the underlying molecular mechanisms still need validation and clarification.…”