COVID-19 Phytochemicals: Study Shows That Plant Flavonols Such As Myricitrin And Myricetin Could Be Potential Antivirals Against The SARS-CoV-2 Virus

COVID-19 Phytochemicals: Scientist from the University of Batna-Algeria in a new study with findings published in the peer reviewed European Journal of Pharmacology, have found that the phytochemicals belonging to the class of flavonols that are found commonly in many plants and vegetables could be used as a therapeutic approach to COVID-19. The flavonols myricitrin and myricetin-3-O-β-D-glucopyranoside especially had great potential to be utilized as therapeutics with antiviral properties towards the SARS-CoV-2 coronavirus. https://www.sciencedirect.com/science/article/pii/S0014299920308517


 
Thailand Medical News has already been utilizing these phytochemicals myricitrin and myricetin extracted from the leaves of the sweet potato plant in our Therapeutic Teas For COVID-19  which is to date the only herbal prophylactic and therapeutic compound that has the highest amounts of herbs and phyto- chemicals used in a single herbal preparation against the SARS-CoV-2 coronavirus, each with its own proven and supporting studies and to date the only herbal compound that has demonstrated proper and positive results in a  variety of observational studies across the world including in countries like Colombia, Peru, Brazil, Argentina, India, Iran, Canada, Pakistan, Bangladesh, China, Italy and Spain and in much smaller aspects with doctors in the U.S. We are hoping to start randomized trials hopefully next year once we can secure proper fundings.https://www.thailandmedical.news/news/new-therapeutic-teas-
 
The flavonols myricitrin and myricetin demonstrate a variety of antiviral, anti-inflammatory and immunomodulatory properties.
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772053/
 
https://pubmed.ncbi.nlm.nih.gov/25546350/
 
https://www.tandfonline.com/doi/full/10.1080/14756366.2020.1754813
 
https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-017-0183-6
 
Although the compound is genotoxic if used correctly it can be used even for DNA induced changes or for epigenetic purposes. https://focusontoxpath.com/lectures/Genotoxicity-evaluation-flavonoid-myricitrin-aglycone-myricetin.pdf
 
The current COVID-19 caused by the SARS-CoV-2 coronavirus represents the actual greatest global public health crisis. The lack of efficacious drugs and vaccines against this viral infection created a challenge for scientific researchers in order to find effective solutions. One of the promising therapeutic approaches is the search for phytochemicals and bioactive molecules with few side effects that display antiviral properties in natural sources like medicinal plants and vegetabl es. The antioxidant, anti-inflammatory, and antiviral activities of flavonoids have led many researchers to investigate the effects of these biomolecules on SARS-CoV-2.
 
Several computational and experimental studies indicated that flavonoids especially flavonols and their derivatives constitute effective viral enzyme inhibitors and possess interesting antiviral activities.
 
Among natural compounds, the flavonoids class and flavonols constitutes a possible target for antiviral drugs due to its large spectrum of biological properties (antioxidant, anti-inflammatory and antiviral properties)
https://www.researchgate.net/profile/Prithviraj_Karak2/publication/333448824_BIOLOGICAL_ACTIVITIES_OF_FLAVONOIDS_AN_OVERVIEW/links/5cee616f299bf1c50e8531f3/BIOLOGICAL-ACTIVITIES-OF-FLAVONOIDS-AN-OVERVIEW.pdf
 
https://www.sciencedirect.com/science/article/abs/pii/S0163725818301748
 
https://www.mdpi.com/1999-4915/12/2/184
 
This class of secondary metabolites occurs abundantly in a variety of medicinal plants, fruits and vegetables. Indeed, onions, kale, lettuce, tomatoes, apples, grapes and berries are considered as rich sources of flavonoids. https://www.mdpi.com/2223-7747/9/6/800
 
https://www.mdpi.com/2223-7747/9/6/800
 
Flavonol is one of the most important classes of flavonoids characterized by a hydroxyl group in C-3 position of the C ring. According to data analysis, flavonols constitute the most studied compounds against coronavirus.
https://www.sciencedirect.com/science/article/pii/S0009279720307948
 
https://www.mdpi.com/1420-3049/25/17/3980
 
https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1690480
 
https://europepmc.org/article/med/32819226
 
Indeed, kaempferol, quercetin, myricetin, fisetin and their derivatives were the most documented molecules with antiviral activities against SARS-CoV-2. Also, these molecules had a broad spectrum of biological activities (anti-HIV, antioxidant, anti-inflammatory and cardiovascular protective effects), that could reduce the severity of infection symptoms and enhance the immune response of the patient. https://onlinelibrary.wiley.com/doi/abs/10.1002/9780470015902.a0027666
 
https://www.mdpi.com/1420-3049/25/4/1017
 
https://www.tandfonline.com/doi/abs/10.1080/10715762.2020.1813887
 
In this context, the present study reviews the efficacy of many dietary flavonols as potential antiviral drugs targeting the SARS-CoV-2 enzymes and proteins including Chymotrypsin-Like Protease (3CLpro), Papain Like protease (PLpro), Spike protein (S protein) and RNA-dependent RNA polymerase (RdRp), and also their ability to interact with the angiotensin-converting enzyme II (ACE2) receptor. The relationship between flavonol structures and their SARS-CoV-2 antiviral effects were highlighted in this study. On the other hand, the immunomodulatory, the anti-inflammatory and the antiviral effects of secondary metabolites from this class of flavonoids were also reported. Also, their bioavailability limitations and toxicity were predicted.
 
Numerous past studies have demonstrated that many dietary flavonols disrupt the ability of SARS-CoV-2 to bind to its target host cell receptor angiotensin-converting enzyme 2 (ACE2) and gain viral entry. https://www.mdpi.com/1420-3049/25/11/2707
 
https://www.sciencedirect.com/science/article/pii/S0014299920305409
 
https://biointerfaceresearch.com/wp-content/uploads/2020/08/20695837111.84828501.pdf
 
The study also discusses how some flavonols can inhibit the activity of SARS-CoV-2 proteins that are involved in viral replication.
 
Lead researcher Dr Chaima Mouffouk from the University of Batna told Thailand Medical News, “These molecules may alleviate the severity of COVID‐19 symptoms and modulate the immune response.”
 
Flavonols ie the most prevalent group of flavonoids are of particular interest to researchers and their antiviral activity against SARS-CoV-2 has been well documented, say Dr Mouffouk and colleagues.
 
The study team have now reviewed some of the evidence published between January and August this year (2020) demonstrating the potential of flavonols as antiviral agents for targeting SARS-CoV-2.
 
These flavonols can target essential viral proteins, including 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), Spike protein (S protein) and RNA-dependent RNA polymerase (RdRp). They can also interact with the ACE2 receptor that SARs-CoV-2 uses to enter host cells. https://science.sciencemag.org/content/368/6492/779.abstract
 
https://www.sciencedirect.com/science/article/abs/pii/S0924857920301709
 
https://www.scielo.br/scielo.php?pid=S0074-02762020000100341&script=sci_arttext
 
Often referred to as the main protease, 3CLpro is an enzyme involved in the proteolytic maturation of viral polypeptides that form a protein complex called RNA replicase-transcriptase complex. This complex is essential for viral transcription and replication. 
 
The study team says that molecules that target 3CLpro may be able to prevent post-translational processing of SARS-CoV-2 polypeptides and reduce the risk of mutation-mediated drug resistance. https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1690480
 
https://pubs.rsc.org/lv/content/articlehtml/2020/ra/d0ra03582c
 
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240653
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156227/
 
The PLpro is also an important proteolytic enzyme that cleaves viral polyproteins to form a number of nonstructural viral proteins. In addition, PLpro has been shown to inhibit the production of interferons, which exert antiviral activity.  
 
The team says that molecules that inhibit PLpro would induce an antiviral response in host cells and also disrupt the replication cycle.
 
https://www.tandfonline.com/doi/full/10.1080/14756366.2016.1265519
 
https://www.researchgate.net/profile/Manisha_Gurnani/publication/340675622_Potential_Phytochemicals_as_Efficient_Protease_Inhibitors_of_2019-nCoV/links/5ead6e2845851592d6b27575/Potential-Phytochemicals-as-Efficient-Protease-Inhibitors-of-2019-nCoV.pdf
 
https://pubs.acs.org/doi/abs/10.1021/acs.jpclett.0c00994
 
https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1761883
 
https://lavierebelle.org/IMG/pdf/2020_potential_inhibitor_of_covid-19_main_protease_from_several_medicinal_plant_compounds.pdf
 
The study that tested 32,297 molecules used in traditional Chinese medicine, found that the flavonols myricitrin and myricetin-3-O-β-D-glucopyranoside showed a strong binding affinity for the receptor-binding site of 3CLpro.
 
https://www.sciencedirect.com/science/article/pii/S2095177920301271
 
Dr Mouffouk said, “These compounds are also non-toxic, biologically active and naturally found in many medicinal species.”
 
The research also showed that the flavonols astragalin, kaempferol, and quercetin, all consistently interacted with both 3CLpro and PLpro. These molecules all exhibited stronger binding affinities for the two enzymes than the drug remdesivir. (Remdesivir is a claimed ‘antiviral cum  immunomodulatory agent’ approved for use by the U.S. FDA as a COVID‑19 treatment in around fifty countries that is overpriced and to date has shown no efficacy and was basically a scam tat is speculated to be perpetrated by the Trump administration, the NIH lead by Dr Anthony Fauci and also a clandestine group of businessmen lead by billionaire Tom Cahill.) https://www.sciencedirect.com/science/article/pii/S2095177920301271
 
https://chemrxiv.org/articles/preprint/In_Silico_Docking_Analysis_Revealed_the_Potential_of_Phytochemicals_Present_in_Phyllanthus_Amarus_and_Andrographis_Paniculata_Used_in_Ayurveda_Medicine_in_Inhibiting_SARS-CoV-2/12751361/1
 
The Spike or S protein is the main viral structure that SARS-CoV-2 uses to bind to ACE2 and fuse with the host cell membrane. Molecules that could block this binding of S to ACE2 would prevent the virus from entering host cells.
 
A recent study reported that the flavonols fisetin, quercetin, isorhamnetin and kaempferol had a higher binding affinity for the S protein than the drug hydroxychloroquine, which has been investigated as a potential treatment for COVID-19. https://biointerfaceresearch.com/wp-content/uploads/2020/08/20695837111.84828501.pdf
 
https://chemrxiv.org/articles/In-Silico_Identification_of_Potent_Inhibitors_of_COVID-19_Main_Protease_Mpro_and_Angiotensin_Converting_Enzyme_2_ACE2_from_Natural_Products_Quercetin_Hispidulin_and_Cirsimaritin_Exhibited_Better_Potential_Inhibition_than_Hydroxy-Chloroquine/12181404
 
Another study found that the myricetin could interact with ACE2 and cause conformational changes that inhibited viral entry. https://www.mdpi.com/1420-3049/25/11/2707
 
The RdRp is an enzyme involved in the synthesis of viral RNA and is essential to viral replication and transcription.
 
A past molecular docking study showed that quercetin and kaempferol, as well as the glucuronide and sulfate derivatives of these flavonols, potently inhibited the RdRp protein. An analysis of binding energy values showed that a number of quercetin derivatives demonstrated higher binding affinities than quercetin itself, says the study team. https://www.scielo.br/scielo.php?pid=S0074-02762020000100341&script=sci_arttext
 
Dr Mouffouk and the study team says the evidence reviewed in this study suggests that flavonols may represent a promising new therapeutic strategy for COVID-19.
 
Dr Mouffouk added, “Flavonols have the ability to disturb and destabilize the binding between S protein and ACE2, leading to the inhibition of virus entry, and halt the activity of several enzymes involved in viral replication including 3CLpro, PLpro and RdRp.”
 
The study team concluded, “Due to their large spectrum of biological activities, these molecules may alleviate the severity of COVID‐19 symptoms and modulate the immune response.”
 
It is also important to note that since most of these flavonols are basically from plants and most even found in common vegetables and plants that we consume in our diets, hence they are relatively safe and non-toxic if used correctly.
 
For more on COVID-19 Phytochemicals, keep on logging to Thailand Medical News.