UPLC–PDA–ESI–qTOF-MS profiling and potent anti-HSV-II activity of Eucalyptus sideroxylon leaves

•UPLC–MS analysis allowed the identification of 70 metabolites in E. sideroxylon (Myrtaceae) leaves•Phloroglucinol-rich extract (PGRE) was found to be non-cytotoxic (CC50 is 0.808 mg/mL).•Potent antiviral activity was observed against HSV-II (87.65% inhibition).•PGRE decrease HSV-II replication and attachment on VERO cells.•Weak antiviral activity against HSV-I (8.88%) and no activity against CoxB4 and hepatitis A viruses were reported. Eucalyptus is one of the most important and highly exploited genus in family Myrtaceae. An UPLC/PDA/ESI-qTOF-MS method was adopted to identify Eucalyptus sideroxylon Cunn. ex Woolls leaves phytoconstituents. Cytotoxicity of E. sideroxylon leaves phloroglucinol-rich extract (PGRE) on VERO cells was determined. The antiviral effect of PGRE against hepatitis A (HAV), herpes simplex type 1 (HSV-I), herpes simplex type 2 (HSV-II), coxsackie (CoxB4), and adenoviruses was in vitro evaluated using MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide). UPLC–MS analysis allowed the identification of 70 metabolites including: 26 triterpenes, 13 phloroglucinols, 8 fatty acids, 5 flavonoids, 5 oleuropeic acid glucosides, 3 gallic acid derivatives, and 10 miscellaneous. Twenty four metabolites identified in the leaves of E. sideroxylon and four in the genus Eucalyptus are reported herein for the first time. PGRE was found to be non-cytotoxic; the concentration that reduced the cell viability by 50% (CC50) was 0.808mg/mL. Maximum non-toxic concentration (MNTC) of PGRE on Vero cells was 0.312mg/mL. The best antiviral activity was observed against HSV-II. Its mechanism was through decreasing the viral replication (IC50 189.36μg/mL, 87.65% inhibition) and attachment on Vero cells (IC50 199.34μg/mL, 83.13% inhibition) rather than virucidal effect (IC50 293.1μg/mL, 50.68% inhibition). This study provides a complete map for E. sideroxylon leaves composition. It also suggests the plant as a source of new antiviral agents.