Geranium and Lemon Essential Oils and Their Active Compounds Downregulate Angiotensin-Converting Enzyme 2 (ACE2), a SARS-CoV-2 Spike Receptor-Binding Domain, in Epithelial Cells

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease-2019 (COVID-19), is a pandemic disease that has been declared as modern history’s gravest health emergency worldwide. Until now, no precise treatment modality has been developed. The angiotensin-converting enzyme 2 (ACE2) receptor, a host cell receptor, has been found to play a crucial role in virus cell entry; therefore, ACE2 blockers can be a potential target for anti-viral intervention. In this study, we evaluated the ACE2 inhibitory effects of 10 essential oils. Among them, geranium and lemon oils displayed significant ACE2 inhibitory effects in epithelial cells. In addition, immunoblotting and qPCR analysis also confirmed that geranium and lemon oils possess potent ACE2 inhibitory effects. Furthermore, the gas chromatography-mass spectrometry (GC–MS) analysis displayed 22 compounds in geranium oil and 9 compounds in lemon oil. Citronellol, geraniol, and neryl acetate were the major compounds of geranium oil and limonene that represented major compound of lemon oil. Next, we found that treatment with citronellol and limonene significantly downregulated ACE2 expression in epithelial cells. The results suggest that geranium and lemon essential oils and their derivative compounds are valuable natural anti-viral agents that may contribute to the prevention of the invasion of SARS-CoV-2/COVID-19 into the human body.

Comparison of Chemical Composition between Kuromoji (Lindera umbellata) Essential Oil and Hydrosol and Determination of the Deodorizing Effect

“…1,8-Cineole is abundantly present in eucalyptus plants and is an effective treatment for pediculosis [ 15 ], as well as an efficient biological herbicide [ 16 ], antimicrobial, and antioxidant [ 17 ]. Recently, several essential oil-derived components, such as 1,8-cineole, have been reported to inhibit influenza symptoms [ 18 ] and severity of coronavirus disease 2019 (COVID-19) [ 19 , 20 , 21 ]. Furthermore, some researchers are also investigating using 1,8-cineole as a new treatment for COVID-19 symptoms [ 22 , 23 ].…”

GB-2 inhibits ACE2 and TMPRSS2 expression: In vivo and in vitro studies

“…Many natural compounds have been screened as therapeutic candidates for COVID-19 treatment through in silico molecular docking method [ 18 ]. Kumar et al reported that geranium, lemon oils, and the major compounds of lemon oils (citronellol and limonene) exhibited significant ACE2 inhibitory effects in epithelial cells [ 36 ]. Withanone, a compound from the alcoholic extract of Ashwagandha, could inhibit the mRNA expression of TMPRSS2 in MCF-7 cells [ 35 ].…”

Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury

“…Currently, there is no clinically used ACE2-based therapeutic agent; however, preclinical studies and clinical trials are continuing [ 25 , 317 , 332 ]. Several natural products , including flavonoids, e.g ., apigenin, quercetin, baicalin and epigallocatechin, and anthraquinones, e.g ., emodin (for a review [ 333 ]), and geranium and lemon essential oils [ 334 ] were reported to inhibit ACE2 activity in in vitro assays. Nicotianamine, isolated from soybean, was described to be a potent inhibitor of human ACE2 with an IC 50 of 84 nM [ 335 ].…”