Discovering Traditional Chinese Medicine (TCM) Formulas for Complex Diseases Based on a Combination of Reverse Systematic Pharmacology and TCM Meridian Tropism Theory: Taking COVID-19 as an Example.

Objective: Infections and death have been a part of our daily lives since the COVID-2019 pandemic outbreak in 2019, and the societal and economic consequences have lingered for an unanticipated duration. Novel and effective treatments are still desperately needed around the world to combat the infection. Here, we discovered a novel traditional Chinese medicine formula (TCMF) to potentially combat COVID-19 through reverse systematic pharmacology (disease → targets → TCMF → disease).

Methods: Combining Integrative network pharmacology and the traditional Chinese medicine (TCM) theory, a TCMF for COVID-19 was identified. physiological interactions between herbs and disease hub targets were validated by molecular docking and dynamics simulation.

Results: Based on disease-related gene/pathway targets and a combination of reverse pharmacology and TCM meridian tropism theory, a COVID-19-associated herb database was constructed. A new TCMF, including Gancao, Baitouweng, Congbai, and Diyu (GBCD), was discovered for anti-COVID-19 therapy. The KEGG and GO analyses of 49 intersecting genes suggested that GBCD could combat COVID-19 through antiviral, antiinflammation, immunoregulation, and cytoprotection activities. Moreover, these possible effects were validated through docking and MD simulation.

Conclusions: To the best of our knowledge, this study is the first to combine reverse pharmacology and meridian tropism theories for TCMF development, and a novel herbal combination, GBCD, was discovered for anti-COVID-19 therapy.