Antiviral Activity of Haematococcus pluvialis Algae Extract Is Not Exclusively Due to Astaxanthin

In this study, astaxanthin, which has previously been shown to have antiviral effects, was examined for its dose-dependent potency to inhibit cellular SARS-CoV-2 infections. Naturally occurring astaxanthin is obtained and orally administered as ASX-oleoresin, a composition of different astaxanthin fatty acid esters. We therefore hypothesized that the compound's beneficial effects are not only related to astaxanthin. Thus, a "green" algae extract (i.e., poor astaxanthin content < 0.2%; ASX^p) of the microalgae Haematococcus pluvialis, as well as an astaxanthin-rich algae extract (astaxanthin content = 20%; ASX^r), were tested in in vitro cellular viral infection assays. Thereby, it was found that both extracts reduced viral infections significantly. As a potential mode of inhibitory action, the binding of ASX-oleoresin to the viral spike protein was investigated by isothermal fluorescence titration, revealing binding affinities of Kd = 1.05 µM for ASX^r and Kd = 1.42 µM for ASX^p. Based on our data, we conclude that several ASX-oleoresin fractions from H. pluvialis exhibit antiviral activity, which extends beyond the known antioxidant activity of astaxanthin. From a molecular dynamic simulation of ASX-oleoresin, fatty acid domains could be considered as activity-chaperoning factors of ASX. Therefore, microalgae biomass should be considered in the future for further antiviral activities.