Pomegranate peel extract has shown potential as an inhibitor of SARS-CoV-2 virus

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes COVID-19 (Coronavirus Disease 2019), has infected more than 58.5 million people worldwide and killed more than 1.38 million people. This is one of the most serious global health crises in recent memory. Currently, there are no effective and safe vaccines to prevent SARS CoV-2 infection, nor effective drugs to treat COVID-19 disease. Therefore, researchers around the world are trying to find effective molecules and compounds that may help fight the virus.

Researchers led by Relja Suručić, lead author of the Faculty of Medicine, Banja Luka University, studied the use of pomegranate skin extracts in the prevention of SARS-CoV-2 infection. Their study, entitled “Computational Study of Pomegranate Peel Extract Polyphenols as Potential Inhibitors of SARS-CoV-2 Virus Internalization,” was published in the latest issue of the journal. Molecular and cell biochemistry..

Background

Coronavirus, Explains researchers and is known to cause respiratory tract infections in humans. These include the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and the novel coronavirus SARS-CoV-2. SARS-CoV-2 is known to cause serious symptoms in some individuals who require hospitalization, ventilation, and ICU care.World Health Organization Declares COVID-19 Pandemic on 11th^th In March of this year.

Virus structure, infection and infection

The SARS-CoV-2 virus also has a high rate of transmission between humans. The virus has four major structural proteins, along with other accessory proteins.

• Spike (S) Glycoprotein
• Small envelope (E) glycoprotein
• Membrane (M) glycoprotein
• Nucleocapsid (N) protein

SARS-CoV-2 uses S glycoproteins to enter airway cells. The virus interacts with the angiotensin converting enzyme 2 (ACE2) receptor, which is abundant in the respiratory system.

S glycoproteins have two functional subunits, known as the amino (N) -terminal subunit S1 and the carboxyl (C) -terminal subunit S2. Surface S1 binds to the ACE2 receptor, and S2 interacts with the host cell membrane, allowing the cell membrane to fuse with the virus, allowing viral particles to eventually invade the cell. Host cells contain specific proteases that disrupt or cleave S1 / S2, allowing the process of fusion and invasion. A notable protease is the transmembrane serine protease 2 (TMPRSS2). Both ACE2 and TMPRSS2 are required for virus entry into cells.

Flynn also causes cleavage of the S glycoprotein and promotes SARS-CoV-2 virus invasion by binding to the ACE2 receptor. TMPRSS2 and furin inhibitors are speculated to prevent the virus from invading host cells.

Pomegranate skin extract

Several natural products are being investigated to prevent or effectively treat SARS-CoV-2 infection. pomegranate (pomegranate L., The Punicaceae family, which is consumed worldwide, has beneficial health properties and is known to be useful in the treatment of type 2 diabetes, atherosclerosis, cardiovascular disease, inflammatory disease, cancer and more.

Pomegranate peel extracts are known to contain “plant organisms such as hydrolyzable tannins (ellagitannin, punicalin, punicalin, gallic acid, ellagic acid), flavonoids, anthocyanins and other phenols”. I will. These polyphenols are known to have several properties, including:

• Anti-inflammatory effect
• antioxidant effect
• Hypoglycemia or blood sugar lowering effect
• Lipid-lowering or cholesterol-lowering effect
• Antihypertensive or antihypertensive effect
• Antibacterial effect

Researchers say that pomegranate extracts are known to be useful against viruses such as “influenza virus, herpesvirus, poxvirus, and human immunodeficiency virus.” Molecules in the extract called “punicalin, punicalin, ellagic acid” are also effective against hepatitis C virus (HCV). Pomegranate peel extract (PoPEx) has also been shown to be effective against influenza virus by preventing viral invasion and RNA transcription.

In this study, we focused on the four major ellagitannin members present in PoPEx: punicalin, punicalin, ellagic acid, and gallic acid. Effectiveness For SARS-CoV-2, a lab model (in silico tool).

Study design

Researchers tested the binding affinities of ellagic acid, gallic acid, punicalin, and punicalin against four protein targets that the virus could invade host cells. These molecules tested are:

• Umi Fenoville
• Lopinavir
• Camostat, and
• Selected PoPEx components (punicalin, punicalin, ellagic acid, gallic acid)

The four ptoieitn targets are:

• SARS-CoV-2 spike glycoprotein,
• Angiotensin converting enzyme 2,
• Furin,
• Transmembrane serine protease 2 (TMPRSS2).

The 3D structures of the tested molecules were downloaded and their binding affinity was checked using computational techniques.

result

The results of this study show that components of pomegranate skin extracts such as punicalin and punicalin have great potential for interaction with selected protein targets and therefore may prevent viral invasion into host cells. Showed that there is. This should be followed up in the in vitro and in vivo studies they wrote.

• Using the DoGSiteScorer tool, potential binding pockets were determined on the protein.
• The most draggable pockets of S glycoprotein, ACE2, furin, and TMPRSS2 were selected.
• High non-polar amino acid ratio (non-polar amino acid ratio is 0.63), which means an excellent drug discovery target for S glycoproteins
• The non-polar amino acid ratios for ACE2, furin and TMPRSS2 were 0.38, 0.26 and 0.40, respectively.
• The best drug score values ​​for the analyzed targets ranged from 0.73 to 0.84.
• The pocket volume of drug binding has determined the likelihood that the drug will bind to the target. The most important volumes, surfaces, and depths of the selected pockets were detected by ACE2.
• Punicalin and punicalin formed the most stable complex with protein targets.They also showed strong interactions with TMPRSS2 amino acid residues.

Conclusions and implications

Preventing virus invasion into host cells can effectively prevent infection. This study showed that PoPEx polyphenols can provide potential inhibitory activity against SARS-CoV-2, especially during its invasion of host cells. The author of the study wrote, “Punicalin and punicalin are promising candidates for further anti-SARS-CoV-2 in vitro studies.” The team concluded, “Because it is a natural product ingredient used in foods, these candidates also have a confirmed safety profile, which is an additional important benefit in disease treatment.”