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

Herein, the antibacterial, antifungal and antiviral activities of Astragalus spinosus 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 Bacillus cereus, Klebsiella pneumoniae, and Pseudomonas aeruginosa 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-O-rutinoside and isorhamnetin-O-rutinoside showed superior activity against the MATE receptor, however, isorhamnetin-O-rutinoside and rutin-7-O-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-O-rutinoside and isorhamnetin-O-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-O-rutinoside, and rutin-7-O-hexoside showed superiorities over the co-crystal ligands of HSV-1 thymidine kinase by almost 20 and 13 kcal/mol, respectively.