Chemical Compositions of Clove (Syzygium aromaticum (L.) Merr. & L.) Extracts and Their Potentials in Suppressing SARS-CoV-2 Spike Protein–ACE2 Binding, Inhibiting ACE2, and Scavenging Free Radicals

Abstract

COVID-19 is initiated by binding the SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2) on host cells. Food factors capable of suppressing the binding between the SARS-CoV-2 spike protein and ACE2 or reducing the ACE2 availability through ACE2 inhibitions may potentially reduce the risk of SARS-CoV-2 infection and COVID-19. In this study, the chemical compositions of clove water and ethanol extracts were investigated, along with their potentials in suppressing SARS-CoV-2 spike protein−ACE2 binding, reducing ACE2 availability, and scavenging free radicals. Thirty-four compounds were tentatively identified in the clove water and ethanol extracts, with six reported in clove for the first time. Clove water and ethanol extracts dosedependently suppressed SARS-CoV-2 spike protein binding to ACE2 and inhibited ACE2 activity. The water extract had stronger inhibitory effects than the ethanol extract on a dry weight basis. The clove water extract also had more potent free radical scavenging activities against DPPH • and ABTS •+ (536.9 and 3525.06 μmol TE/g, respectively) than the ethanol extract (58.44 and 2298.01 μmol TE/g, respectively). In contrast, the ethanol extract had greater total phenolic content (TPC) and relative HO • scavenging capacity (HOSC) values (180.03 mg GAE/g and 2181.08 μmol TE/g, respectively) than the water extract (120.12 mg GAE/g and 1483.02 μmol TE/g, respectively). The present study demonstrated the potential of clove in reducing the risk of SARS-CoV-2 infection and COVID-19 development.

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 water extract WE33.3 (33.3 mg dry cinnamon equivalents/mL in the testing mixture) completely inhibited the binding interaction between SARS-CoV-2 spike protein and ACE2, significantly higher than the 33.51% inhibition of the water extract WE1.7 (1.7 mg dry cinnamon equivalents/mL in the testing mixture) (Figure A). These results are comparable to that of clove water extracts (99% for WE33.3 and 46% for WE1.7) . As for the ethanol extract (Figure B), the ethanol extract EE3.3 (3.3 mg dry cinnamon equivalents/mL in the testing mixture) significantly inhibited 98.73% of the interaction between SARS-CoV-2 spike protein and ACE2 (Figure B).…”

“…The clove water extract inhibited 100% (WE5.0) and 82% (WE0.5), which was more potent than the cinnamon water extract (98.83% for WE5.0 and 10.51% for WE0.5). Interestingly, the clove ethanol extract possessed strong potency (91% for EE5.0) but had no inhibition for the lower concentration (0% for EE0.5), while the cinnamon ethanol extract possessed 97.24% for EE5.0 and 18.03% for EE0.5 . This is the first report of cinnamon extracts’ inhibition of ACE2 activity.…”

“…Among the ways to suppress COVID-19 infection, blocking the entry of the virus via interaction between spike protein and ACE2 has recently been considered a promising approach . Cinnamon water and ethanol extracts dose-dependently inhibited the binding interaction between SARS-CoV-2 spike protein and ACE2 (Figure ).…”

“…The inhibitory effects of cinnamon water and ethanol extracts on the binding interaction between SARS-CoV-2 spike protein and ACE2 were investigated using a commercial assay kit (No. 502050, Cayman, Ann Arbor, Michigan USA) . The assay was conducted based on the manufacturer’s instructions.…”

“…The inhibitory effects of cinnamon extracts on ACE2 were investigated with a commercial assay kit (No. 502100, Cayman, Ann Arbor, Michigan USA) following the manufacturer’s instructions . The concentrations of the cinnamon extracts in the testing mixture were 5.0 and 0.5 mg dry cinnamon equivalents/mL based on preliminary study results.…”