In Vitro Antiviral Potential of Syzygium Species Extracts Against Dengue Virus Serotype 2

Background: Dengue is a vector-borne disease caused by four serotypes of dengue virus (DENV), spread rapidly through Aedes mosquito bites in tropical and subtropical regions. Due to the unavailability of approved antiviral treatment for dengue, continued effort to discover antiviral candidates from natural resources is in need. Purpose: In this study, Syzygium myrtifolium (stems) and Syzygium grande (leaves and stems) extracts were assessed for their cytotoxicity and antiviral activity against DENV2 in vitro. Methods: The antiviral properties of methanolic extracts of S. myrtifolium (stem) and S. grande (leaves and stem) were determined by exposing the serially diluted extracts on DENV2-infected African green monkey kidney (Vero) and human hepatocellular carcinoma (Huh-7). The infection rate was measured by an immunofluorescence-based high-content screening technique. The synthesis of virus progeny was measured by a plaque assay. The ATP-based luminescent assay was used to determine the cytotoxicity effect of the extracts on Vero cells and Huh-7. Results: Low cytotoxicity effects of S. myrtifolium (stem) and S. grande (leaves and stem) extracts were shown in Huh-7 and Vero cells with CC₅₀ ranges from >133 to 67.36 μg/mL. The extracts of S. myrtifolium stems, S. grande leaves and S. grande stems showed potent antiviral activities at the pre-infection phase in Vero cells with EC₅₀ of 5.57, 5.37 and 10.13 μg/mL, respectively. At the post-infection phase, S. myrtifolium stem and S. grande leaf and stem extract treatments also resulted in infection-inhibitory effects with EC₅₀ of 15.01, 13.45 and 10.33 μg/mL, respectively. However, reduced antiviral activities of the extracts were observed in Huh-7 cells with EC₅₀ ranges from 40.23 to 82.83 μg/mL. Conclusions: This study provides scientific evidence on Syzygium myrtifolium and Syzygium grande as promising candidates for further investigation in the development of dengue antivirals.