Isolation of Metabolites With Antiviral Activity From the Brown Algae Dictyota fasciola and Dictyota mediterranea

Twenty diterpenes (1-20) and a sesquiterpene (21) were isolated from Dictyota fasciola and Dictyota mediterranea collected from the Aegean Sea and evaluated as potential antiviral agents against a panel of viral pathogens. Among the isolated metabolites, six dolabellane diterpenes (1-4, 9, and 12) and one germacrane sesquiterpene (21) are new natural products. The evaluation of the antiviral activity of the isolated compounds was carried out against three viruses of different phylogenetic backgrounds that are characterized by high incidence in human population and cause significant medical threat and economic losses worldwide: herpes simplex virus (HSV-1), human coronavirus (HCoV-NL63), and Zika virus (ZIKV). The antiviral assays demonstrated that some compounds inhibited the viruses within a concentration range of 3-10 µg/mL. The maximal suppression of viral replication was 90% for HSV-1, 99.99% for HCoV-NL63, and 96.8% for ZIKV, highlighting the differential efficacy of the tested compounds against specific viruses. Mechanistic studies revealed that, depending on the compound, antiviral activity occurred either at the virus attachment stage or during a post-entry replication stage. Among the tested compounds, metabolites 6-8, 13, 17, and 18 exhibited considerable antiviral activity against RNA (HCoV-NL63, ZIKV) and DNA (HSV-1) viruses.