Flavonoid Profiling, Molecular Docking, and Modulatory Effects of <i>Artemisia herba- alba</i> Leaf Extract on ACE2 and TMPRSS2 Gene Expression

Several studies have reported the potential antiviral activity of Artemisia species, which is related mainly to their flavonoid constituents. Transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) are critical SARS-CoV-2 entry factors. In this study, the phytochemical composition and modulatory effects of Artemisia herba-alba leaf extract on the gene expression of ACE2 and TMPRSS2 were investigated. To identify the flavonoid profile, HPLC was used. Cytotoxicity was estimated in A549 carcinoma and HDFn fibroblasts using an MTT assay (IC50 = 114.8 μg/mL). The real-time PCR results revealed significant upregulation of TMPRSS2 gene expression (2.4-fold, p ≤ 0.01; p value = 0.0011), whereas ACE2 expression remained unchanged. Furthermore, a molecular docking study suggested the potential binding affinity of hesperidin and rutin for TMPRSS2 and ACE2. Therefore, both in vitro and in silico results indicated that A. herba-alba extract may interact with the viral entry pathway.