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.

K J Senthil Kumar,Yu-Chien Chen,M Gokila Vani,Ching-Hsiang Huang,Chung-Shuan Wang,Sheng-Yang Wang,Chien-Sing Lai,Li-Ping Lu,Chia-Chi Chen

doi:10.3390/plants9060770

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.

Highlights

Coronaviridae or coronaviruses are a large family of viruses that can cause disease in mammals and birds
The first genomic sequence of COVID-19 was released, and through comparing to the genomes of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, researchers found that COVID-19 has better genomic sequence homology with SARS-CoV than that of MERS-CoV [2,3]
Prior to investigation of the angiotensin-converting enzyme 2 (ACE2) inhibitory effect of essential oils, we determined the cytotoxicity of essential oils on HT-29 cells by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)

Summary

Introduction

Coronaviridae or coronaviruses are a large family of viruses that can cause disease in mammals and birds. The viruses cause illness, ranging from common cold to severe respiratory diseases. In 2002, severe acute respiratory syndrome (SARS) emerged, and in 2012, Middle East respiratory syndrome (MERS) emerged—both are betacoronoviruses transmitted from animal to human that result in severe respiratory diseases in affected individuals [1]. During the first SARS-CoV outbreak, Li et al [4] identified angiotensin-converting enzyme (ACE2) as the human host factor or cell entry receptor for SARS-CoV. Overexpression of ACE2 and injection of SARS-CoV spike protein developed severe acute lung failure in mice, which can be attenuated by blocking the renin-angiotensin pathway [5].

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