Advancing the Identification of Bioactive Molecules and the Construction of a Synergistic Drug Delivery System in Combating Lung Injury

Abstract In recent years, pneumonia caused by multiple viruses has posed a significant threat to public health, particularly affecting vulnerable populations such as the elderly and immunocompromised individuals. Current treatments primarily focused on antiviral medications, lacking “miracle cure” and innovative approaches for the pathological damage caused by viruses. Since 2019, Traditional Chinese Medicine (TCM) has shown remarkable efficacy in treating coronavirus disease 2019 (COVID‐19). However, the application is hindered by intricate mechanisms, variable quality, and slow onset. Clinically, Ge‐Gen Decoction (GGD) effectively reduced the severity in patients with viral infections. Taking COVID‐19 as a case, the bioactive ingredients from GGD: glabridin (GLA) and puerarin (PUE) are identified. Interestingly, it was discovered that PUE can self‐assemble into a 3D hydrogel structure upon heating and cooling, namely PUE@gel. This process mirrored the formation of gel‐like precipitates in GGD post‐decoction. Motivated by this phenomenon, a decoction‐mimicking drug delivery system, glabridin─puerarin self‐assembled hydrogel (GLA‐PUE@gel) was constructed, which exhibits strong anti‐inflammatory and antioxidant properties, comparable to GGD at the same dosage. Additionally, PUE that has a high biosafety threshold can competitively bind to angiotensin converting enzyme 2 (ACE2) on host cells, preventing SARS‐CoV‐2 from invading. This study offered a promising approach for treating virus‐induced lung injury.