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The application of traditional Chinese medicine (TCM) has made great contributions to the fight against the epidemic of coronavirus disease-2019 (COVID-19).Despite the remarkable therapeutic effects of TCM, the molecular mechanisms of TCM formulae inhibiting COVID-19 are still not fully understood.Here, we combined the automated high throughput sequencing-based high throughput screening (HTS2) assay with bioinformatics and computer-aided drug design (CADD) to investigate the molecular mechanisms of TCM-mediated therapeutic effects on COVID-19-related cytokine storm (Fig.1a).