In conclusion, we demonstrate for the first time that four small molecules of quercetin, glabridin, gallic acid and chrysoeriol may serve as novel and robust therapeutic options for COVID-19 by: (1) inhibiting viral entry into endothelial cells through downregulation of ACE2/TMPRSS2; (2) preserving endothelial function via attenuation of excessive superoxide production elicited by S protein activation of NOX2; and (3) abolishing endothelial inflammation by blocking S protein induction of pro-inflammatory protein MCP-1. The gene discussed is ACE2; the disease is COVID-19.