Discovery of intervention effect of Chinese herbal formulas on COVID-19 pulmonary fibrosis treated by VEGFR and FGFR inhibitors

Abstract

Since February 2020, a large number of patients infected with new coronavirus has been cured and discharged with the controlling of epidemic. Pulmonary fibrosis, which may be one of the sequela caused by COVID-19, not only brings dyspnea and deterioration of lung function, but also affects patients' life because of its high mortality and poor prognosis. Vascular endothelial growth factor receptor(VEGFR) and fibroblast growth factor receptor(FGFR) can inhibit the proliferation, activation and migration of fibroblasts by regulating the signal transduction pathway involved in the process of pulmonary fibrosis. Chinese herbal formulas pose a good therapeutic effect on pulmonary fibrosis. Present study explores the intervention effect on pulmonary fibrosis of traditional Chinese medicine(TCM) by screening the potential inhibitors of VEGFR and FGFR. The docking models of VEGFR and FGFR were established to obtain the potential active ingredients which were filtered by the docking score. According to 2 prescriptions in the Protocol for the diagnosis and treatment of coronavirus disease 2019(7th edition)and 9 prescriptions in Traditional Chinese medicine prescriptions for treating blight, 959 and 1 047 potential ingredients were obtained as the inhibitors of VEGFR and FGFR respectively with the screening thres-hold set as eighty percent of the docking score of the initial ligands. The potential herbs were then filtered by the components with a hit rate higher than 30%, such as Scutellariae Radix, Adenophorae Radix, Pinelliae Rhizoma, Coicis Semen, etc. To discuss the rule of TCM in the treatment of pulmonary fibrosis, the networks of TCM-channel tropism and TCM-efficacy of the potential herbs was constructed. The potential herbs for treating pulmonary fibrosis mostly belong to lung(degree=14) and spleen(degree value=8), and the efficacy is focused on reinforcing deficiency(degree=9). Qiyin Prescription and Buzhong Yiqi Decoction contain the largest number of the potential herbs. The main symptom of COVID-19 is damp-heat stagnating in the lung, which always causes impairment of body fluid and Qi. Clinical observation shows that patients in the recovery period are mostly at the status that the remaining virus toxicity is not exhausted while the vital Qi have not recovered. The results of this study are expected to provide references for clinical medication in preventing and treating pulmonary fibrosis caused by COVID-19.