Qingqi Guxue Decoction induces S cell cycle arrest to inhibit replication of severe fever with thrombocytopenia syndrome virus

Severe fever with thrombocytopenia syndrome (SFTS) is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV), characterized by high fever and thrombocytopenia. It has been proved that traditional Chinese medicine (TCM) has displayed definite therapeutic effects on viral hemorrhagic fever, indicating its potential to treat SFTS. In this study, SFTS-relative key targets were predicted via gene ontology (GO) analysis and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Molecular docking was then used to select stable binders. Molecules matched TCMs were identified, and a new prescription, Qingqi Guxue decoction (QQGX), was formulated to clear heat and nourish blood, with a resulting drug composition network. We explored the optimal drug proportion for QQGX. Through an in-depth study of molecular mechanisms, we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2 (CCNA2) and cyclin-dependent kinase 2 (CDK2), thereby inhibiting SFTSV replication. Finally, we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV. In summary, our study prepared a TCM decoction using the method of network pharmacology. This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.