COVID-19, a novel coronavirus, severely damages lung function and disrupts the immune system, leading to the release of a large number of pro-inflammatory cytokines and the development of a “cytokine storm,” which can result in fatal acute respiratory distress syndrome (ARDS). Survivors of COVID-19 may face irreversible pulmonary fibrosis and lifelong disabilities. To address this, we established a drug screening platform for COVID-19 to investigate whether existing drugs, particularly traditional Chinese medicine formulas like YQ1, could target the unique characteristics of COVID-19 compared to other respiratory viruses (MERS-CoV and SARS-CoV).
Gene set enrichment analysis (GSEA) revealed that YQ1, a traditional Chinese medicine formula mainly composed of Huangqi, can reverse SARS-CoV-2 infections and suppress the development of cytokine storms, thereby inhibiting the development of ARDS. Biochemical studies demonstrated that YQ1 stimulates let-7a, miR-148a/b, and miR-146a, leading to the inhibition of virus replication and the release of pro-inflammatory cytokines, as well as promoting macrophage polarization towards the antiviral M1 phenotype and controlling intracellular oxidative stress. YQ1 showed efficacy in treating ARDS induced by bleomycin and preventing its progression in a rat model. Significant improvements in arterial oxygen saturation, respiratory rate, and lung morphology were observed in the experimental rats.
Furthermore, YQ1 was used to treat 21 hospitalized COVID-19 patients, including 3 ARDS patients, at Chang Gung Hospital, and all of them were discharged. This demonstrates the value and benefits of our innovative research and its (1) unique predictive platform system for prioritizing old drugs for COVID-19 patients and future outbreaks, and (2) the potential of YQ1 as a promising drug for the prevention and early intervention therapy of COVID-19.
