Ability of natural flavonoids to inhibit SARS-CoV-2

A recent systematic review discusses naturally occurring flavonoids as a promising antiviral alternative to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, this review calls for further evaluation of flavonols, quercetin, myricetin, and their derivatives, flavon baicalins and baicaleins, flavan-3-olepigallocatechin gallates (EGCGs), and their flavonoids such as tannic acid. I will report. In vivo Use and clinical studies.

study: Promising antiviral activity of natural flavonoids against SARS-CoV-2 targets: systematic review.. Image Credit: DIVA.photo / Shutterstock.com

Preface

Humans in the last 20 years coronavirus The SARS-CoV-1 epidemic in 2003, the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in 2012, and the recent ongoing coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. ) Caused the epidemic. All of these viruses belong to the genus Betacoronavirus, along with the common cold-causing human coronaviruses HCoV-OC43 and HCoV-HKU1.

SARS-CoV-2 alone caused enormous global distress with blockages, national closures, morbidity and mortality. To date, more than 247 million confirmed cases of COVID-19 have been reported, including more than 5 million deaths.

Zoonotic virus attacks, unequal distribution of vaccines, and the emergence of new SARS-CoV-2 strains have supported global efforts to find potential inhibitors of major viral processes. rice field.

The development of both antiviral drugs and efficient therapeutic strategies is a long and tedious process, and most of these drugs are single-target drugs designed for unique viral enzymes. Therefore, natural substances are often considered attractive alternative therapeutic solutions, as these compounds are also a major source of antibacterial and antiviral drugs.

What are flavonoids?

Flavonoids are natural substances that have been shown to act on coronavirus enzymes, which are essential drug targets, through a complementary approach through both. In silico With virtual screening In vitro experiment.

Flavonoids are hydroxylated phenolic plant molecules that belong to secondary plant metabolites from fruits, vegetables, roots, and other plant products such as tea and wine. The various subclasses of flavonoids include anthocyanins, chalcones, dihydrochalcones, dihydroflavonols, flavan-3-ols, flavanones, flavonols, flavonols, flavanonols, and isoflavonoids.

Flavonoids protect plant cells from pathogens, insects and other stressful environments. Functionally, flavonoids have been shown to have antibacterial, antioxidant, anti-inflammatory, antimutagenic, anticancer, and antiviral properties.

These compounds are safe, highly bioavailable, non-systemic toxic, block multiple pathways with functional groups and interact with a variety of targets. Interestingly, about 194 countries participate in national-level policies for Chinese herbal medicine, using flavonoids as potential and easy candidates for epidemics and pandemics.

In the current study, reviewers emphasize that the flavonoid antiviral activity demonstrated in previous studies emphasizes the importance of exploring these natural products against SARS-CoV-2. doing. To better understand the role of flavonoids as antiviral agents, reviewers first described the biology and pathogenesis of SARS-CoV-2 and current therapeutic strategies for the treatment of COVID-19 infection. ..

Flavonoids have emerged as a safe alternative therapeutic strategy for different targets to block the coronavirus life cycle at different stages of viral infection. In this regard, reviewers have presented several possible targets in viral and infected hosts that can be developed to inhibit the viral etiology of SARS-CoV-2.

Antiviral properties of flavonoids against coronavirus

The flavonoids kaempferol, chrysin, and quercetin act against both human and bovine coronaviruses (BCVs). Theafluflavin inhibits BCV, while quercetin 7-ramnoside inhibits the non-respiratory coronavirus porcine epidemic diarrhea virus (PEDV).

Multiple polyphenols, especially chalcone Broussochalcone B, effectively inhibit MERS-CoV cysteine ​​proteases such as 3CLpro and papain-like protease (PLpro). Herbacetin, isobaba chalcone, quercetin 3-β-d-glucoside, and helicricetin also showed anti-MERS-CoV3CLpro activity.

Taken together, over 69 flavonoids have been identified for their inhibitory activity against specific SARS-CoV-2 targets. Therefore, reviewers presented a summary of these flavonoids, isolated based on subclasses and inhibition targets. The most promising SARS-CoV-2 targets for these flavonoids include 3CLpro, followed by viral spike (S) protein-angiotensin converting enzyme (ACE2) receptors and the involved nonstructural protein PLpro. it was done. In proteolytic cleavage.

Specifically, the authors of this study tabulated the antiviral activity of flavonols and flavanonols reported for SARS-CoV-23CLpro. In vitro A methodology separated for each class. The most promising flavanol is epigallocatechin gallate (EGCG) for 3CLpro activity.

Flavones such as baicalin, baicalin, seturarain, wagonin, wogonoside, oroxylin, flavanones such as naringenin, and isoflavones such as puerarin, daidzein, and genistin were active against the protease 3CLpro.

Combining flavonoid mixtures or encapsulating active compounds to increase the uptake of hydrophilic flavonoids is some of the various methods employed in various studies and established significant viral inhibition. There are some results.

Flavonoids are also used for important interactions in the viral life cycle. In this interaction, the viral S protein binds to the human ACE2 receptor during the viral invasion phase. Reviewers have tabulated a range of flavonoids with antiviral activity mediated by inhibition of this interaction. Some of them include isorhamnetin, quercetin, rutin, tamalixetin, (±) -eriodictyol, pinocembrin, and epicatechin (EC).

The reviewers also described the antiviral activity of flavonoids against other lesser-studied SARS-CoV-2 targets in various cell-based methodologies. These mechanisms of action include inhibition of SARS-CoV-2 endoribonuclease nsP15, RNA-dependent RNA polymerase (RdRp), membrane protein genes, decreased ribonucleic acid (RNA) levels of nucleocapsid protein genes, and SARS-CoV-2. Includes inhibition of replication. It blocks mitochondrial OXPHOS and targets 2-well channel 2 (TPC2) of endolysosomes.

Flavonoid structure-activity relationship (SAR)

The authors of the current study discuss the structure-activity relationship of flavonoid subclasses, including flavanols, flavanonols, flavones, flavanones, flavanols, and isoflavones, with the interaction of SARS-CoV-2 3CLpro, PLpro, S proteins, and hACE2 receptors. Was also discussed. Overall, the authors reported that the presence of hydroxyl groups in all rings of flavonoids increased their activity.

Specifically, myricetin was found to be the most effective flavonoid against its most promising target, 3CLpro. Myricetin has six hydroxyl groups that spread over three phenolic rings. The authors also investigated the effects of group substitution, polarity, electronegativity, and their effective activity.

Conclusion

The reviews described here introduce natural flavonoids as a promising alternative, based on findings collected from previously published studies.In addition, researchers focused on data from In vitro Study on the effects of flavonoids on SARS-CoV-2 targets such as 3CLpro, papaine-like protease (PLpro), S protein-ACE2 interaction, helicase, nucleocapsid (N) protein.

In summary, reviewers reported quercetin and myricetin derivatives such as baicalein, baicalin, and tannic acid as the most promising flavonoids for SARS-CoV-2 targets.