Antiviral effect of fucoxanthin obtained from Sargassum siliquastrum (Fucales, Phaeophyceae) against severe acute respiratory syndrome coronavirus 2

Abstract

Human coronavirus diseases, particularly severe acute respiratory syndrome coronavirus 2, still remain a persistent public health issue, and many recent studies are focusing on the quest for new leads against coronaviruses. To contribute to this growing pool of knowledge and explore the available marine natural products against coronaviruses, this study investigated the antiviral effects of fucoxanthin isolated from Sargassum siliquastrum—a brown alga found on Jeju Island, South Korea. The antiviral effects of fucoxanthin were confirmed in severe acute respiratory syndrome coronavirus 2-infected Vero cells, and its structural characteristics were verified in silico using molecular docking and molecular dynamic simulations and in vitro colorimetric method. Fucoxanthin inhibited the infection in a concentration-dependent manner, without showing cytotoxicity. Molecular docking simulations revealed that fucoxanthin binds to the angiotensinconverting enzyme 2-spike protein (binding energy -318.306 kcal mol<sup>-1</sup>) and main protease (binding energy -205.118 kcal mol<sup>-1</sup>). Moreover, molecular dynamic simulations showed that fucoxanthin remains docked to angiotensin-converting enzyme 2-spike protein for 20 ns, whereas it breaks away from main protease after 3 ns. Also, the in silico prediction of the fucoxanthin was verified through the in vitro colorimetric method by inhibiting the binding between angiotensinconverting enzyme 2 and spike protein in a concentration-dependent manner. These results indicate that fucoxanthin exhibits antiviral effects against severe acute respiratory syndrome coronavirus 2 by blocking the entry of the virus. Therefore, fucoxanthin from S. siliquastrum can be a potential candidate for treating coronavirus infection.