Polyphenols Could Prevent SARS-CoV-2 Infection by Modulating the Expression of miRNAs in the Host Cells

Milenkovic, Dragan; Ruskovska, Tatjana; Rodriguez-Mateos, Ana; Heiss, Christian

Coronaviruses (CoVs) are single-stranded RNA viruses which following virus attachment and entry into the host cell, particularly type 2 pneumocytes but also endothelial cells, release RNA into cytosol where it serves as a matrix for the host translation machinery to produce viral proteins. The viral RNA in cytoplasm can interact with host cell microRNAs which can degrade viral RNA and/or prevent viral replication. As such host cellular miRNAs represent key cellular mediators of antiviral defense. Polyphenols, plant food bioactives, exert antiviral properties, which is partially due to their capacity to modulate the expression of miRNAs. The objective of this work was to assess if polyphenols can play a role in prevention of SARS-CoV-2 associated complications by modulating the expression of host miRNAs. To test this hypothesis, we performed literature search to identify miRNAs that could bind SARS-CoV-2 RNA as well as miRNAs which expression can be modulated by polyphenols in lung, type 2 pneumocytes or endothelial cells. We identified over 600 miRNAs that have capacity to bind viral RNA and 125 miRNAs which expression can be modulated by polyphenols in the cells of interest. We identified that there are 17 miRNAs with both the capacity to bind viral RNA and which expression can be modulated by polyphenols. Some of these miRNAs have been identified as having antiviral properties or can target genes involved in regulation of processes of viral replication, apoptosis or viral infection. Taken together this analysis suggests that polyphenols could modulate expression of miRNAs in alveolar and endothelial cells and exert antiviral capacity.