The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells

Contact between SARS-CoV-2 and human lung cells involves the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, the latter being strongly involved in the regulation of inflammation as well as blood pressure homeostasis. SARS-CoV-2 infection is characterized by a strong inflammatory response defined as a "cytokine storm". Among recent therapeutic approaches against SARS-CoV-2 targeting the dramatic inflammatory reaction, some natural products are promising. Diatoms are microalgae able to produce bioactive secondary metabolites, such as the xanthophyll diatoxanthin (Dt). The aim of this study is to demonstrate the anti-inflammatory effects of Dt on the A549-hACE2 lung cell line, exploring its interaction with the ACE2 receptor, as well as depicting its role in inhibiting a cytokine storm induced by the SARS-CoV-2 spike glycoprotein. Results showed that Dt enhanced the cell metabolism, e.g., the percent of metabolically active cells, as well as the ACE2 enzymatic activity. Moreover, Dt strongly affected the response of the SARS-CoV-2 spike glycoprotein-exposed A549-hACE2 cells in decreasing the interleukin-6 production and increasing the interleukin-10 release. Moreover, Dt upregulated genes encoding for the interferon pathway related to antiviral defense and enhanced proteins belonging to the innate immunity response. The potential interest of Dt as a new therapeutic agent in the treatment and/or prevention of the severe inflammatory syndrome related to SARS-CoV-2 infection is postulated.