This study evaluated the chemical composition of rosemary water extract (RWE) and its influence on mechanisms by which the SARS-CoV-2 virus enters into cells as a potential route for reducing the risk of COVID-19 disease. Compounds in RWE were identified using UHPLC-MS/MS. The inhibitory effect of RWE was then evaluated on binding between the SARS-CoV-2 spike protein (S-protein) and ACE2 and separately on ACE2 activity/availability. Additionally, total phenolic content (TPC) and free radical scavenging capacities of RWE against HO•, ABTS•+, and DPPH• were assessed. Twenty-one compounds were tentatively identified in RWE, of which tuberonic acid hexoside was identified for the first time in rosemary. RWE dose of 33.3 mg of rosemary equivalents (RE)/mL suppressed the interaction between S-protein and ACE2 by 72.9%, while rosmarinic and caffeic acids at 3.3 μmol/mL suppressed the interaction by 36 and 55%, respectively. RWE at 5.0, 2.5, and 0.5 mg of RE/mL inhibited ACE2 activity by 99.5, 94.5, and 68.6%, respectively, while rosmarinic acid at 0.05 and 0.01 μmol/mL reduced ACE2 activity by 31 and 8%, respectively. RWE had a TPC value of 72.5 mg GAE/g. The results provide a mechanistic basis on which rosemary may reduce the risk of SARS-CoV-2 infection and the development of COVID-19.
Keywords: ACE2; Rosemary; SARS-CoV-2; UHPLC-MS; antioxidant; spike protein.