We found that quercetin, glabridin, gallic acid, or chrysoeriol treatment of endothelial cells attenuated viral S protein-induced upregulation in ACE2, active TMPRSS2, NOX2, MCP-1 and superoxide production, indicating therapeutic potential of these small molecule compounds for COVID-19 via preservation of endothelial function. Here, ACE2 is linked to COVID-19.