Researchers in Italy have conducted a study demonstrating the potential antiviral effects of pomegranate extract against severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19).
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The team found that constituents in extracts obtained from pomegranate peels (PPE) inhibited the binding of SARS-CoV-2 to the human host cell receptor angiotensin-converting enzyme 2 (ACE2) in vitro.
PPE compounds also inhibited the activity of the SARS-CoV-2 main protease 3CL pro, which the virus needs to replicate and survive within the host cell.
Although further studies will be determinant to assess the efficacy of this extract in vivo, our results open up new promising opportunities to employ natural extracts for the development of effective and innovative therapies in the fight against SARS-CoV-2,”
Fabio Apone, Arterra Bioscience SPA
A pre-print version of the paper is available on the bioRxiv* server, while the article undergoes peer review.
One of the most serious pandemics in human history
Since SARS-CoV-2 was first identified in Wuhan, China, late last year (2019), its unprecedented spread has led to one of the most serious pandemics in human history.
The COVID-19 pandemic has now caused more than 64.1 million infections worldwide and claimed the lives of more than 1.48 million people.
While the infection usually only causes mild symptoms, some individuals develop a severe disease that causes multiple organ damage.
SARS-CoV-2 mainly targets tissues that express high levels of ACE2 – the human receptor that the virus uses to gain host cell entry.
Since the airways express high levels of ACE2, individuals who experience severe disease often develop viral pneumonia or acute respiratory distress syndrome, which can lead to respiratory failure.
Although significant efforts have been made to develop therapeutic strategies, no effective drugs or vaccines are yet available.
The main viral structure SARS-CoV-2 uses to access host cells is the surface Spike protein, which attaches to the ACE2 receptor via its receptor-binding domain.
Inhibiting Spike and ACE2 binding still represents one of the most popular strategies for controlling SARS-CoV-2,”
Where might plants compounds come in?
Plant extracts are rich in bioactive molecules such as polyphenols that play vital roles in plant survival by protecting against pathogens such as bacteria, viruses, and fungi.
Several studies have previously demonstrated the antiviral potential of some types of polyphenols against a range of viral infections, including influenza, Epstein-Barr virus, and herpes simplex virus.
Several reports of the potential antiviral activity of plant extracts against SARS-CoV-2 infection have also suggested that plant polyphenols could be potential drug candidates for COVID-19 treatments.
Many molecular docking studies have suggested that polyphenols such as curcumin, kaempferol, catechin, naringenin, and quercetin may inhibit the activity and replication of SARS-CoV-2.
“One study also suggested that the binding of two polyphenols, punicalagin, and theaflavin, to the Spike protein, could be exploited as a strategy to inhibit the virus entry into human cells,” write Apone and colleagues.
Furthermore, several studies investigating the antiviral effects of PPE on influenza and the herpes simplex virus have led researchers to hypothesize that these extracts may contain components that are effective against SARS-CoV-2.
What did the researchers do?
Apone and team used in vitro techniques to assess the potential antiviral activity of PPE against SARS-CoV-2.
Punicalagin was the most abundant polyphenol in the PPE, representing 38.9 % of all the polyphenols. This was followed by pedunculagin anomers (16.7%) and punicalin anomers (13.2%).
Using an inhibitor screening kit, the researchers showed that three concentrations of PPE, ranging from 0.04 mg/mL to 1 mg/mL, inhibited the interaction between Spike and ACE2 by up to 74%, in a dose-dependent manner.
Further analysis of PPE’s components revealed that punicalagin was the most effective compound at disrupting this interaction, inhibiting 49% of the Spike–ACE2 binding. This was followed by ellagic acid which inhibited 36% of the interaction.
The researchers also found that incubation of the viral main protease 3CL pro with PPE inhibited the activity of the enzyme by up to 80%.
Punicalagin was again the most effective compound, inhibiting about 50% of this enzymatic activity, while ellagic acid only inhibited about 10%.
What are the study implications?
The researchers say the findings suggest that PPE may play multiple biological roles in reducing the ability of SARS-CoV-2 to infect host cells.
“The study here presented paves the way for a deeper investigation on the activity of pomegranate peel polyphenols in preventing SARS-CoV-2 infection in vivo and it may also promote new ideas on how to reuse agroindustry byproducts for medical and health care applications,” concludes the team.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Apone F, et al. A pomegranate peel extract as inhibitor of SARS-CoV-2 Spike binding to human ACE2 (in vitro): a promising source of novel antiviral drugs. bioRxiv, 2020. doi: https://doi.org/10.1101/2020.12.01.406116