Music Muscle Mindfulness Heartfulness Happiness Health Fitness Fashion Phytonutrients


Role of polyphenols in combating the SARS COVID-19 pandemic

Posted on December 25, 2021 at 2:30 AM

Role of polyphenols in combating the SARS COVID-19 pandemic

Potential therapies for SARS-CoV-2 can be categorized into two groups based on targets; drugs that target the virus and drugs that target the host and its immune system.83 The target proteins in SARS-CoV-2 are categorized as non-structural proteins (MPRO, PLPRO and RdRp) and spike protein (S protein) (Table 1). Resveratrol, a well-known phytoalexin, showed potent inhibitory action against MERS-CoV in an in vitro study. The same study also indicated that resveratrol could prolong the cellular survival after viral infection.84 Emodin, an anthraquinone polyphenol found in the roots of rhubarb, was found to inhibit the interaction of ACE2 and S protein (Table 1).85 Molecular docking studies have shown that polyphenols from Curcuma sp. (curcumin and its derivatives) and Citrus sp. (hesperetin, hesperidin, and tangeretin) have a stronger binding affinity for the S protein than the reference compound nafamostat.86

Naringenin was found to have more substantial binding energy to viral spike glycoprotein (PDB: 6VSB) than remdesivir,87 an anti-viral which was approved by the FDA for the therapy of COVID-19.88 Tetra-O-galloyl-β-D-glucose (TGG) and luteolin were found to bind with SARS-CoV surface protein and thus hinder the virus's entry into the host cell.89
The target for the binding of the SARS-CoV-2 is the ACE2, which is a transmembrane metallocarboxypeptidase.90 This receptor thus serves as a potential target for anti-viral drug discovery.

Eriodictyol, a flavanone found in Eriodictyon californicum, showed the highest affinity for ACE2 among 77 candidates.91 Although in silico studies can identify promising candidates, more in vitro and in vivo studies are required to assess their actual impact on the pandemic. A study found that mice having inactivated or knocked-out ACE2 developed severe SARS-CoV infection, and they sustained lung injury worse than the wild type control group. The symptoms were alleviated upon administration of recombinant ACE2.92 A cell-based assay revealed that the entry of both SARS-CoV and SARS-CoV-2 was blocked when soluble ACE2 was introduced, thus confirming that recombinant ACE2 can be used as a decoy target against viral S protein.93,94

Since ACE2 plays a vital role in human physiology, targeting it for anti-viral drug discovery should be done after careful assessment of its risks. Protease inhibitors are a class of compounds that have been extensively used in the management of viruses like HIV, MERS-CoV and SARS-CoV.95,96 The structural and non-structural proteins essential for the life cycle of the coronavirus are proteolytically processed from the polyprotein by 3CLPRO (MPRO) and the PLPRO.97

Natural products like diarylheptanoids,98 terpenoids,99 flavonoids100 and coumarins100 are potent inhibitors of the SARS-CoV proteases. In silico and in vitro analyses have found that epigallocatechin gallate (IC50 = 73 μM), gallocatechin gallate (IC50 = 47 μM) and quercetin (IC50 = 73 μM) are potent inhibitors of the SARS-CoV-2 MPRO.101,102

Flavonoids such as kaempferol and isoliquiritigenin synergistically inhibited the SARS-CoV-2 MPRO and PLPRO in vitro.103 Gentile et al. screened a library of Marine Natural Products (MNP Library) and identified potent inhibitors of the SARS-CoV-2 MPRO via molecular docking analysis. The potent inhibitors of the viral MPRO were heptafuhalol A, phlorethopentafuhalol B, pseudopentafuhalol C, phlorethopentafuhalol A, hydroxypentafuhalol A and pentaphlorethol B, 1,3,5-trihydroxybenzene from Sargassum spinuligerum and 8,8′-bieckol, 6,6′-bieckol and dieckol from Ecklonia cava.104 Flavonoids from traditional Chinese medicines, like herbacetin, rhoifolin, and pectolinarin, were found to inhibit the MPRO of SARS-CoV.105 Jo et al. found that flavonoids like herbacetin, isobavachalcone and helichrysetin have an inhibitory effect on MERS-CoV MPRO.106

Wen et al. investigated over 200 plant extracts to find their inhibitory effect on SARS-CoV. SARS-CoV induced cytopathogenic effects were studied in Vero E6 cell lines and they have shown that herbal extracts from Gentianae radix, Dioscoreae rhizoma, Cassiae semen and Loranthi ramus and Rhizoma cibotii in the concentrations from 25 to 200 μg ml−1 proved to have a potential inhibitory effect on SARS-CoV.107

A recent in silico study on naturally derived compounds came up with 3 potential leads which can block the entry of the SARS-CoV-2 in the host cells by inhibiting the host target protein TMPRSS2. The same study also showed that the three compounds (glucogallin, mangiferin, and phlorizin) could also be used to restrict the virus's life cycle inside the host due to their inhibitory action on the viral MPRO.108 The possible anti COVID-19 mechanism of action of the above-mentioned compounds in this section are compiled in a column in Table 2.

Indexed for Royal Society Of Chemistry by Dragonfly Kingdom Library

Categories: Dragonfly Kingdom International Service Agency: North East Nature Guard, New England True Sustainability Initiative, Springfield Green Team Partnership: Site Updates, Blog And Improvements, Bright Star Apothecary, Complimentary & Integrative Medicine, U.I. Food News

Post a Comment


Oops, you forgot something.


The words you entered did not match the given text. Please try again.

You must be a member to comment on this page. Sign In or Register