Antiviral Activity of Chlorophyll Extracts from Tetraselmis sp., a Marine Microalga, Against Zika Virus Infection

Recent advancements in the large-scale cultivation of <i>Tetraselmis</i> sp. in Korea have enabled year-round production of this marine microalgae. This study explores the potential industrial applications of <i>Tetraselmis</i> sp. biomass by investigating the antiviral properties of its extracts and primary components. The antiviral effects of <i>Tetraselmis</i> sp. extracts were evaluated in Zika virus (ZIKV)-infected cells. Following extensive isolation and purification, the main compounds were characterized using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) analyses. Their antiviral activities were confirmed using in vitro and in silico tests. <i>Tetraselmis</i> sp. extracts reduced infectious viral particles and non-structural protein 1 messenger RNA levels in ZIKV-infected cells without inducing cytotoxicity. Additionally, they modulated the interferon-mediated immune system responses. <i>Tetraselmis</i> sp. extracts are composed of four main chlorophylls: chlorophyll a, chlorin e₆-13¹-15²-dimethyl-17³-phytyl ester, hydroxychlorophyll a, and hydroxypheophytin a. Among them, chlorophyll a, chlorin e₆-13¹-15²-dimethyl-17³-phytyl ester, and hydroxypheophytin showed the antiviral activities in ZIKV-infected cells and molecular docking simulations predicted interactions between these chlorophylls and ZIKV. Our findings suggest that <i>Tetraselmis</i> sp. chlorophyll extracts exert antiviral effects against ZIKV and could serve as potential therapeutic candidates against ZIKV infection.