Bioactive Compositions of Cinnamon ( Cinnamomum verum J. Presl) Extracts and Their Capacities in Suppressing SARS-CoV-2 Spike Protein Binding to ACE2, Inhibiting ACE2, and Scavenging Free Radicals.

Cinnamon ( Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food and supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, the bioactives in cinnamon water and ethanol extracts were chemically identified, and their potential in suppressing SARS-CoV-2 spike protein-angiotensin-converting enzyme 2 (ACE2) binding, reducing ACE2 availability, and scavenging free radicals was investigated. Twenty-seven and twenty-three compounds were tentatively identified in cinnamon water and ethanol extracts, respectively. Seven compounds, including saccharumoside C, two emodin-glucuronide isomers, two physcion-glucuronide isomers, and two type-A proanthocyanidin hexamers, were first reported in cinnamon. Cinnamon water and ethanol extracts suppressed the binding of SARS-CoV-2 spike protein to ACE2 and inhibited ACE2 activity in a dose-dependent manner. Cinnamon ethanol extract had total phenolic content of 36.67 mg gallic acid equivalents (GAE)/g and free radical scavenging activities against HO • and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS •+ ) of 1688.85 and 882.88 μmol Trolox equivalents (TE)/g, which were significantly higher than those of the water extract at 24.12 mg GAE/g and 583.12 and 210.36 μmol TE/g. The free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH • ) of cinnamon ethanol extract was lower than that of the water extract. The present study provides new evidence that cinnamon reduces the risk of SARS-CoV-2 infection and COVID-19 development.