Investigating the antimicrobial and antiviral activities of <i>Astragalus spinosus</i> (Forssk.) Muschl.: biological assessments and <i>in silico</i> studies

Herein, the antibacterial, antifungal and antiviral activities of <i>Astragalus spinosus</i> leaves, the largest genus in the family Fabaceae, were evaluated. Forty compounds were identified from the hydroalcoholic plant extract using the LCMS/MS technique. The identified candidates were chemically divided into hydroxycinnamic acid derivatives, flavonoids, and their glycosides. The hydroalcoholic extract showed potent antibacterial activity against <i>Bacillus cereus, Klebsiella pneumoniae</i>, and <i>Pseudomonas aeruginosa</i> with MIC between 5 and 10 mg/mL. Moreover, the extract exhibited a considerable antiviral effect against HSV-2 (IC₅₀ = 57.9 µg/mL). Molecular docking studies were performed to get insights into the different binding poses of the identified candidates toward either the MATE or HSV-1 target receptors. Compounds kaempferol-<i>O</i>-rutinoside and isorhamnetin-<i>O</i>-rutinoside showed superior activity against the MATE receptor, however, isorhamnetin-<i>O</i>-rutinoside and rutin-7-<i>O</i>-hexoside achieved the best binding toward the HSV-1 receptor. The stabilities of the best compounds inside the active pocket were investigated using MD simulation and the MM-GBSA binding energies for the studied complexes were also calculated and compared to the native ligands. Kaempferol-<i>O</i>-rutinoside and isorhamnetin-<i>O</i>-rutinoside showed similar binding energies to the co-crystal ligand of the MATE multidrug efflux pump with MM-GBSA energy of -83.94 and -82.27 kcal/mol, respectively. However, isorhamnetin-<i>O</i>-rutinoside, and rutin-7-<i>O</i>-hexoside showed superiorities over the co-crystal ligands of HSV-1 thymidine kinase by almost 20 and 13 kcal/mol, respectively.