COVID-19 Herbs: Phytochemicals Ellagic Acid, Gallic Acid, Punicalagin And Punicalin Extracted From Pomegranate Peels Could Inhibit SARS-CoV-2 Virus

COVID-19 Herbs: In new research by scientists from the faculty of medicine, University of Banja Luka-Bosnia/Herzegovina and the Institute for Medicinal Plant Research Belgrade-Serbia, that involved using computational molecular docking studies, it was found that the phytochemicals Ellagic Acid, Gallic Acid, Punicalagin and Punicalin extracted from pomegranate peels could inhibit the SARS-CoV-2 coronavirus.  


 
The desperate search for an effective COVID-19 therapy has attracted a great deal of scientific interest due to its unprecedented public health care system overload worldwide. As of this evening the total number of global COVID-19 infections has reached 58.8 million while the total number global COVID-19 deaths have reached almost 1.4 million. The situation is fast accelerating and it is not expected that even the vaccines that will be introduced shortly by the tainted American drug regulatory body will offer proper protection against the new SARS-CoV-2 coronavirus strains in circulation and in fact could backfire badly in the later stages. It is best for proponents of these vaccines to have themselves and their loved one vaccinated first and for others to wait for at least 4 to 6 months to see the effects on these individuals.
 
The study team carried out a research to investigate the in silico effects of the most abundant pomegranate peel extract constituents on the multi-step process of SARS-CoV-2 internalization in the host cells. Binding affinities and interactions of ellagic acid, gallic acid, punicalagin and punicalin were studied on four selected protein targets with a significant and confirmed role in the process of the entry of virus into a host cell. The protein targets used in this study were: SARS-CoV-2 spike glycoprotein, angiotensin-converting enzyme 2, furin and transmembrane serine protease 2.
 
The study findings indicated that the constituents of pomegranate peel extracts, namely punicalagin and punicalin had very promising potential for significant interactions with the selected protein targets and were therefore deemed good candidates for further in vitro and in vivo evaluation.
 
The study findings were published in the peer-reviewed journal: Molecular and Cellular Biochemistry. https://link.springer.com/article/10.1007/s11010-020-03981-7
 
The study team  led by first author Dr Relja Suručić from the Department of Pharmacognosy, Faculty of Medicine, University of Banja Luka-Bosnia and Herzegovina, studied the use of pomegranate peel extracts in preventing infections with SARS-CoV-2.
 
Already pomegranate juice is known to possess a variety of antiviral properties. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. https://www.hindawi.com/journals/ecam/2013/606212/
 
https://pubmed.ncbi.nlm.nih.gov/23762148/
 
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179291
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https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-4-41
 
https://www.ajmb.org/Article?id=10395
 
Pomegranate extracts and juice are also known to possess immunomodulatory properties.
 
https://www.alliedacademies.org/articles/antimicrobial-and-immunomodulatory-activity-of-pomegranate-in-the-systemic-candidiasis-on-galleria-mellonella-10708.html
 
https://pdfs.semanticscholar.org/9202/ffa80f6e923aed1f0b2413258c9ca854bfbd.pdf
 
https://www.hindawi.com/journals/ecam/2020/5431350/
 
https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=91256
 
https://www.ijnpnd.com/article.asp?issn=2231-0738;year=2012;volume=2;issue=3;spage=171;epage=184;aulast=Bhandari
 
According to the study team coronaviruses are 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. The SARS-CoV-2 is known to cause severe symptoms in some individuals requiring hospitalization, ventilation, and ICU care.
 
Importantly the SARS-CoV-2 virus also has a rapid transmission rate between humans. The virus has four main structural proteins along with other accessory proteins: 1) spike (S) glycoprotein 2) small envelope (E) glycoprotein 3) membrane (M) glycoprotein and 4) nucleocapsid (N) protein
 
Also important is the fact that the SARS-CoV-2 enters into the cells of the respiratory tract using the S glycoprotein. The SARS-CoV-2 virus interacts with the angiotensin-converting enzyme 2 (ACE2) receptor found abundantly in the respiratory system.
 
The S glycoprotein has two functional subunits known as S1, which is an amino (N)-terminal subunit, and S2, a carboxyl (C)-terminal subunit. S1 on the surface binds to the ACE2 receptor, and the S2 interacts with the host cell membrane to allow the fusion of the membranes of the cell and the virus so that the viral particles can finally enter into the cell. The host cell contains specific proteases that can break or cleave the S1/S2 to allow the process of fusion and entry.A notable protease is the transmembrane serine protease 2 (TMPRSS2). Both the ACE2 and TMPRSS2 are required for viral entry into the cell.
 
Also furin leads to cleavage of the S glycoprotein and thus facilitates the entry of the SARS-CoV-2 virus by its binding to the ACE2 receptor.
 
Significantly TMPRSS2 inhibitors and furin inhibitors are speculated to prevent virus entry into the host cell. https://pubmed.ncbi.nlm.nih.gov/32246845/
 
Presently several herbs and natural products are being explored to prevent SARS-CoV-2 infection or treat it effectively. https://www.thailandmedical.news/articles/covid-19-herbs
 
https://scindeks.ceon.rs/article.aspx?artid=2490-33292002101J
 
The pomegranate fruit (Punica granatum L., Punicaceae family) consumed worldwide has been known to have beneficial health properties and useful in treating type 2 diabetes, atherosclerosis, cardiovascular diseases, inflammatory diseases, cancers, etc. https://pubmed.ncbi.nlm.nih.gov/23684435/
 
https://www.sciencedirect.com/science/article/pii/S1756464619306164
 
https://pubmed.ncbi.nlm.nih.gov/23528829/
 
https://pubmed.ncbi.nlm.nih.gov/30661697/
 
https://www.mdpi.com/2072-6643/9/9/958
 
https://www.sciencedirect.com/science/article/pii/S0023643814001807?via%3Dihub
 
The pomegranate peel extracts are known to contain phytochemicals such as hydrolyzable tannins (ellagitannin, punicalagin, punicalin, gallic and ellagic acid), flavonoids, anthocyanins, and other phenols.
 
Some of these phytochemicals are known to have several properties, including:
-anti-inflammatory effects
-antioxidant effects
-hypoglycaemic or blood sugar reducing effects
-lipid-lowering or cholesterol lowering effects
-antihypertensive or blood pressure lowering effects
-antimicrobial effects
 
https://www.sciencedirect.com/science/article/pii/S1756464619306164
 
https://www.ingentaconnect.com/content/ben/iad/2018/00000012/00000001/art00007
 
https://pubmed.ncbi.nlm.nih.gov/17157465/
 
Importantly pomegranate extracts have been known to be useful against viruses such as “influenza virus, herpes virus, poxviruses, and human immunodeficiency virus. https://pubmed.ncbi.nlm.nih.gov/19586764/
 
https://pubmed.ncbi.nlm.nih.gov/23762148/
 
Phytochemicals in the extract called punicalagin, punicalin and ellagic acid also show effects against hepatitis C virus (HCV). https://pubmed.ncbi.nlm.nih.gov/24958333/
 
Pomegranate peel extracts (PoPEx) have also shown effects against the influenza virus by preventing virus entry and transcription of the RNA. https://pubmed.ncbi.nlm.nih.gov/31908736/
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103433/
 
This silico computational study targeted four major ellagitannin members present in PoPEx ie punicalagin, punicalin, ellagic acid, and gallic acid to gauge their efficacy against SARS-CoV-2 coronavirus.
 
The study team tested the binding affinities of ellagic acid, gallic acid, punicalagin, and punicalin on four protein targets that could allow entry of the virus into the host cell.
 
Besides the selected phytochemicals punicalagin, punicalin, ellagic acid and gallic acid), the drugs Umifenovir, Lopinavir and Camostat were also tested against the four proteins: SARS-CoV-2 spike glycoprotein,Angiotensin-converting enzyme 2,Furin,Transmembrane serine protease 2 (TMPRSS2).
 
In the study, the 3D structures of molecules tested were downloaded, and computational techniques were used to check their binding affinity.
 
The study findings showed that constituents of pomegranate peel extracts such as punicalagin and punicalin show significant potential in interacting with the selected protein targets and thus could possibly prevent the viral entry into the host cell. This needs to be followed up with in vitro and in vivo studies the study team explains.
 
Utilizing the DoGSiteScorer tool, potential binding pockets were determined on the proteins, Subsequently the most druggable pockets for the S glycoprotein, ACE2, furin, and TMPRSS2 were chosen.
 
The study findings showed that for S glycoprotein , the apolar amino acid ratio was 0.63.( A high apolar amino acid ratio means good drug target.)
 
The apolar amino acid ratios of ACE2, furin and TMPRSS2 were 0.38, 0.26 and 0.40, respectively.
 
Importantly the best drug score values for analyzed targets ranged between 0.73 and 0.84
 
Also pocket volumes for drug binding determined the potential of the drug to bind with the target. The most significant volume, surface, and depth of the selected pocket were detected for ACE2.
 
It was found that the phytochemicals punicalagin and punicalin formed the most stable complexes with the protein targets. They also showed intensive interactions with TMPRSS2 amino acid residues
 
Basically the viral entry prevention into the host cell could effectively prevent the infection.
 
This research showed that PoPEx polyphenols could offer potential inhibitory activity against the SARS-CoV-2, especially during its host cell entry.
 
The study team said, “Punicalagin and punicalin are promising candidates for further anti-SARS-CoV-2 in vitro studies. Being the ingredients of a natural product that is used as food, these candidates also have a confirmed safety profile which is their additional and important advantage in the disease treatment.”
 
Herbs and natural products would most likely be the key answers to solving the COVID-19 crisis but until the scientific community and also regulatory bodies and government entities are rid of the influence of the big pharmaceutical and biotech firms that have clandestine billionaires pulling the strings, nothing is going to progress and a lot of research is being suppressed by these greedy entities who would rather peddle expensive toxic drugs with no proven efficacy.
 
We at Thailand Medical have been exploring various herbs and natural products and also conducting certain cutting edge studies that have never been approached before. https://www.thailandmedical.news/news/new-therapeutic-teas-
 
Unfortunately we are based in a ‘screwed’ country where corruption, greed and stupidity are predominant and we do not get any help or assistance from any of the government agencies or the huge local corporations for our research and works. Many other foreign entities simply sit back watch without raising a finger to help and in some cases; they try to copy some of our works which we are fortunate not to reveal too much. To date we only had one generous and kind local donor who helped with our herbal research projects.
 
Lets hope that the COVID-19 crisis really accelerates exponentially and gets worse with more getting infected and dying, then perhaps people might wake up and respond to our calls for help in terms of research and development of herbal products to treat the COVID-19 disease.
 
For more on COVID-19 Herbs, keep on logging to Thailand Medical News.