Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies

Abstract

The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.

Keywords: ACE2; COVID-19; SARS-CoV-2.; medicinal plants; renin-angiotensin-system.

FIGURE 1

Geographical distribution of COVID-19 infection per 100,000 of population across 14-days. Redrawn from source: European Center for disease Prevention and Control (ECDC). Data for September 26, 2020 (European Center for disease Prevention and Control, 2020).

FIGURE 2

Geographical national level policy for herbal medicines among 194 countries. Redrawn from source: WHO Global Report on Traditional and Complimentary Medicine (WHO, 2019).

FIGURE 3

Schematic illustration of SARS-CoV-2 virion and its genome.

FIGURE 4

Schematic drawing of Spike-RBD/TMPRSS2/ACE2 axis. The left half illustrates the native counter-interaction between the RAS pathway and ACE2. The right half highlights four targets of phytomedicine against the Spike-RBD/TMPRSS2/ACE2 axis following SARS-CoV-2 infection. The inset shows the furin cleavage site (-RRAR-) of a spike glycoprotein.

FIGURE 5

Plants and plant products that modulate entry of SARS-CoV-2. The inset shows nicotianamine derived from soy, a product of soybean (Glycine max L.). ACE2, Angiotensin converting enzyme two; RBD, receptor binding domain; TMPRSS2, transmembrane protease serine 2. Phytomedicinal targets of the Spike-RBD/TMPRSS2/ACE2 axis.