Systematic computer analysis of the pharmacology of bioflavonoids in the context of increasing the body's antiviral defenses.

Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment). Objective(s): systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action. Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data. Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail. Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.Copyright © 2023 Modern Medical Technology. All rights reserved.

Combination Chemotherapy with Selected Polyphenols in Preclinical and Clinical Studies-An Update Overview.

This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. According to WHO data, research has been limited to five cancers with the highest morbidity rate (lung, colorectal, liver, gastric, and breast cancer). A systematic review of articles published in the past five years (from January 2018 to January 2023) was carried out with the help of all Web of Science databases and the available base of clinical studies. Based on the preclinical studies presented in this review, polyphenols can enhance drug efficacy and reduce chemoresistance through different molecular mechanisms. Considering the large number of studies, curcumin could be a molecule in future chemotherapy cocktails. One of the main problems in clinical research is related to the limited bioavailability of most polyphenols. The design of a new co-delivery system for drugs and polyphenols is essential for future clinical research. Some polyphenols work in synergy with chemotherapeutic drugs, but some polyphenols can act antagonistically, so caution is always required.

A Review on Therapeutic Potential of Indian Herbal Plants to Counter Viral Infection and Disease Pathogenesis

Herbal plant extracts or purified phytocomponents have been extensively used to treat several diseases since ancient times. The Indian Ayurvedic system and Chinese traditional medicines have documented the medicinal properties of important herbs. In Ayurveda, the polyherbal formulation is known to exhibit better therapeutic efficacy compared to a single herb. This review focuses on six key ayurvedic herbal plants namely, Tinospora cordifolia, Withania somnifera, Glycyrrhiza glabra/Licorice, Zingiber officinale, Emblica officinalis and Ocimum sanctum. These plants possess specific phytocomponents that aid them in fighting infections and keeping body healthy and stress-free. Plants were selected due to their reported antimicrobial and anti-inflammatory effects in several diseases and effectiveness in controlling viral pathogenesis. An ad-vanced literature search was carried out using Pubmed and google scholar. Result(s): These medicinal plants are known to exhibit several protective features against various diseases or infections. Here we have particularly emphasized on antioxidant, anti-inflammatory, anti-microbial and immunomodulatory properties which are common in these six plants. Recent literature analysis has revealed Ashwagandha to be protective for Covid-19 too. The formulation from such herbs can exhibit synergism and hence better effectiveness against infection and related dis-eases. The importance of these medicinal herbs becomes highly prominent as it maintains the har-monious balance by way of boosting the immunity in a human body. Further, greater mechanistic analyses are required to prove their efficacy in fighting infectious diseases like Covid-19. It opens the arena for in-depth research of identifying and isolating the active components from these herbs and evaluating their potency to inhibit viral infections as polyherbal formulations.Copyright © 2023 Bentham Science Publishers.

A review of the health benefits of tea: implications of the biochemical properties of the bioactive constituents

Tea is the second-most drank and refreshing beverage after water since the time immemorial. Tea harbours more than 4000 bioactive compounds viz, different classes of polyphenols, unique amino acid L-Theanine, alkaloids (Caffeine, Theobromine), and Volatile Flavor Compounds (VFC). Tea's polyphenols make its inherent therapeutic potential unlimited. Tea's significance in managing cancer, diabetes, stomach ulcer, influenza, neurological diseases, etc. is well-documented. However, advantageous biochemical capabilities of tea have yet to be fully utilised. Hence, this review aims at to examine tea's variety, drinking habits, biochemistry, and therapeutic qualities. A number of significant online resources, including Google Scholar, PubMed, Science Direct, and others, were searched for various research works on tea and its health-promoting qualities by using keywords like tea, health benefits, bioactive components against diseases, etc. Current review highlighted that drinking a cup or more green tea is recommended for improving antioxidant status and to manage diabetes and obesity related problem. However after detailed review work on tea it become clear that not only green tea but also other varies of tea like black, white tea are also harbour lots of bioactive molecules since they are processed from same plant. Tea improves antioxidant status and manages diabetes and obesity. It also helps prevent and cure, heart disease, malignancy, digestive dysfunction, and metabolic disorders including obesity and diabetes. Epigallocatechin Gallate (EGCG), found in tea, has been shown to reduce complications from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV 2) infection. When taken in its traditional form to manage ailments, tea is sometimes controversial due to a lack of confirming evidence of its benefits. The paper covers the numerous health advantages of tea, focusing on the specific components contributing to such benefits, and stresses the value of diverse brewing processes.

Green Tea Catechins Against COVID-19: Lower COVID-19 Morbidity and Mortality in Countries with Higher per capita Green Tea Consumption

Background: Several vaccines are currently validated for COVID-19 prevention and mass vaccination has already been started in many countries. Nevertheless, it is likely that the development of an efficient therapy that reduces COVID-19 severity/mortality would be still impor-tant for a rather prolonged time, in particular, due to new variants of SARS-CoV-2. Several lines of emerging evidence suggest that green tea catechins such as epigallocatechin-3-gallate have direct anti-viral activity and affect factors associated with COVID-19 severity. Objective(s): Considering that green tea catechins are major constituents of green tea, it may be expected that countries with higher per capita green tea consumption would be less affected by COVID-19. This study assessed this possibility. Method(s): Among countries with a population of at least 3 million (n=134), those with relatively high (above 150 g) per capita green tea consumption have been identified (n=21);(ii) normalized to population values of COVID-19 cases (morbidity) and deaths (mortality) for groups of countries with high and low per capita green tea consumption were compared. Result(s): Striking differences in COVID-19 morbidity and mortality between groups of countries with 'high' and 'low' green tea consumption were found. The differences were still observed after the adjustment for the onset of the disease. An analysis using the multiple linear regression approach suggests that the associations are present at the level of individual countries. Conclusion(s): Results of this study, taken together with emerging pharmacological evidence, suggest that green tea catechins can give valuable clues for the treatment/amelioration of COVID-19.Copyright © 2022 Bentham Science Publishers.

Epigallocatechin Gallate Stabilized by Cyclodextrin Inactivates Influenza Virus and Human Coronavirus 229E.

Natural products are attractive antiviral agents because they are environment-friendly and mostly harmless. Epigallocatechin gallate (EGCg), a type of catechin, is a well-known natural antiviral agent that can inhibit various viruses. However, EGCg easily oxidizes and loses its physiological activity. Although this problem can be overcome by combining EGCg with cyclodextrin (CD-EGCg), which makes it stable in water at high concentrations, the antiviral effect of this compound remains unclear. Here, we show that in Madin-Darby canine kidney (MDCK) and MRC-5 cells, CD-EGCg is cytotoxic for 50% of cells at 85.61 and 65.34 ppm, respectively. Furthermore, CD-EGCg mainly shows its antiviral effect during the adsorption step for all four influenza virus strains (median effect concentration (EC50) was 0.93 to 2.78 ppm). Its antiviral effect post-adsorption is less intense, and no inhibitory effect is observed on influenza viruses pre-adsorption. Moreover, human coronavirus 229E (HCoV-229E) was inhibited at the adsorption step in short contact (EC50 = 2.5 ppm) and long contact conditions (EC50 = 0.5 ppm) by mixing CD-EGCg with HCoV-229E. These results suggest that CD-EGCg effectively inhibits various viruses that require an adsorption step, and is an effective tool for preventing infection.

Un caso di COVID-19 curato con la micoterapia

A COVID-19 patient at the limit of hospitalization (SpO2 at 93%), treated at home, found benefit in the use of antiviral medicinal mushrooms. The main agent would be Cordyceps sinensis, used in traditional Chinese medicine from 620 BC. This fungus has been studied by numerous scientists who have demonstrated its antiviral action against HIV-1, the syncytial respiratory virus, the Coxsackie B3 virus, the A and "H1N1" influenza viruses, the Epstein Barr Virus. This patient treated at a time when treatments with antiretrovirals, enoxaparin or hydroxychloroquine were not yet permitted at home showed an immediate reversal of symptoms after taking Cordyceps sinensis and beta-glucans extracted from other mushrooms. The antiviral properties of the components of the drug used in this clinical case are described through the literature (mini review). The strong point, which would explain the rapid action (if it is not placebo), is the known affinity of the beta-glucans of the medicinal mushroom wall, towards the integrin-based receptors, usually present on neutrophil leukocytes, but also on the "thorns" of the CoV-2. This strong peculiarity that CoV-2 has become a weak point, if we get to inhibit it before it attacks the cells of the respiratory system.

Ayurvedic antiviral agents: Overview of medicinal plants perspective

In recent years, it has been reported that many herbal plants contain antiviral agents which combat a human disease that is caused by pathogenic viruses. The natural products which are obtained from plants as antiviral agents against viruses have gone through researches to check the efficacy and potentials of the herbal products in the prevention of viral disorders. On the basis of randomized controlled studies and in-vivo studies, and in-vitro studies, some agents are utilized all across the globe. Progressively numerous studies on therapy of antivirals have been increased. Though, efficacy remains disputable for antiviral drugs that are employed for viral disorders. The viral diseases are challenging for the health of people around the world cause significant increase in mortality and enhance crises. There are many synthetic antiviral drugs that have a large number of side effects and have narrow therapeutic window range, while in the other hand herbal formulations have minimized side effects. The advantages of herbal formulation over synthetic drugs encourage us to devise and expand new herbal moieties against the emerging viral infections. The medicinal plants contain phytochemicals that have antiviral properties. In this paper, the activity of antiviral agents from medicinal plants which have importance in Ayurveda, are discussed along with their source.

INTERACTION BETWEEN ACE 2 AND SARS-COV2, AND USE OF EGCG AND THEAFLAVIN TO TREAT COVID 19 IN INITIAL PHASES

Covid Virus particles engage with host cells via the ACE-2 and GRP78 receptors, transferring the genome particle to the host cell and transforming it into a replicating machine. RdRP is a key protein in the replication mechanism of all RNA viruses. 3CLpro is a cleavage enzyme that breaks down polyproteins into non-structural polyproteins. All four elements of the Covid viral particle are required for its propagation and action, and blocking any one of them can shut down the entire system. EGCG and Theaflavins are flavonoids that block virus particles from attaching to the host cell's ACE-2 and GRP78 receptors, preventing the genome from being transferred into the cell. EGCG binds to 3CLpro with a molecular docking value of 11.7, while TF3 has a docking score of 10.574, indicating that it prevents host cell contact. TF binds to RdRP with a binding energy of 9.11 kcal/mol, implying that RdRP activities are interfered with. Furthermore, these flavonoids have anti-inflammatory properties and reduce the action of cytokines, which can cause serious respiratory difficulties. Except these two there are many others flavonoids which possess anti-inflammatory and anti-viral properties. All of these data suggest that flavonoids could be a useful treatment for SARS-CoV19;however, the issue of stability and bioavailability arises because it is unstable at lungs pH.

Kombucha - An ancient fermented beverage with desired bioactivities: A narrowed review.

Kombucha, originated in China 2000  years ago, is a sour and sweet-tasted drink, prepared traditionally through fermentation of black tea. During the fermentation of kombucha, consisting of mainly acidic compounds, microorganisms, and a tiny amount of alcohol, a biofilm called SCOBY forms. The bacteria in kombucha has been generally identified as Acetobacteraceae. Kombucha is a noteworthy source of B complex vitamins, polyphenols, and organic acids (mainly acetic acid). Nowadays, kombucha is tended to be prepared with some other plant species, which, therefore, lead to variations in its composition. Pre-clinical studies conducted on kombucha revealed that it has desired bioactivities such as antimicrobial, antioxidant, hepatoprotective, anti-hypercholestorelomic, anticancer, anti-inflammatory, etc. Only a few clinical studies have been also reported. In the current review, we aimed to overhaul pre-clinical bioactivities reported on kombucha as well as its brief compositional chemistry. The literature data indicate that kombucha has valuable biological effects on human health.

Effect of Extraction Methodology on the Phytochemical Composition for Camelia sinensis “Powdered Tea Extracts” from Different Provenances

(1) Background: beverages based on extracts from Camellia sinensis are popular worldwide. Due to an increasing number of processed teas on the market, there is a need to develop unified classification standards based on chemical analysis. Meanwhile, phytochemical characterizations are mainly performed on tea samples from China (~80%). Hence, data on teas of other provenances is recommended. (2) Methods: in the present investigation, we characterized lyophilised extracts obtained by infusion, maceration and methanolic extraction derived from tea samples from China, Japan, Sri Lanka and Portugal by phytochemistry (catechins, oxyaromatic acids, flavonols, alkaloids and theanine). The real benefits of drinking the tea were analysed based on the bioavailability of the determined phytochemicals. (3) Results: the infusions revealed the highest total phenolic contents (TPC) amounts, while methanolic extracts yielded the lowest. The correlation matrix indicated that the levels of phenolic compounds were similar in the infusions and methanolic samples, while extractions made by maceration were significantly different. The differences could be partially explained by the different amounts of (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG) and gallic acids (GA). The catechin percentages were significantly lower in the macerations, especially the quantity of EGCG decreases by 4- to 5-fold after this process. (4) Conclusions: the results highlight the importance of the processing methodology to obtain “instant tea”;the composition of the extracts obtained with the same methodology is not significantly affected by the provenance of the tea. However, attention should be drawn to the specificities of the Japanese samples (the tea analysed in the present work was of Sencha quality). In contrast, the extraction methodology significantly affects the phytochemical composition, especially concerning the content of polyphenols. As such, our results indicate that instant tea classification based on chemical composition is sensible, but there is a need for a standard extraction methodology, namely concerning the temperature and time of contact of the tea leaves with the extraction solvent.

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols.

The abundance of polyphenols in edible plants makes them an important component of human nutrition. Considering the ongoing COVID-19 pandemic, a number of studies have investigated polyphenols as bioactive constituents. We applied in-silico molecular docking as well as molecular dynamics supported by in-vitro assays to determine the inhibitory potential of various plant polyphenols against an important SARS-CoV-2 therapeutic target, the protease 3CLpro. Of the polyphenols in initial in-vitro screening, quercetin, ellagic acid, curcumin, epigallocatechin gallate and resveratrol showed IC50 values of 11.8 µM to 23.4 µM. In-silico molecular dynamics simulations indicated stable interactions with the 3CLpro active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used to measure the binding of polyphenols to 3CLpro in real time. Therefore, we provide evidence for inhibition of SARS-CoV-2 3CLpro by natural plant polyphenols, and suggest further research into the development of these novel 3CLpro inhibitors or biochemical probes.

Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor.

BACKGROUND: As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. RESULTS: We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. CONCLUSIONS: These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

Entry-inhibitory role of catechins against SARS-CoV-2 and its UK variant.

BACKGROUND: The global pandemic caused by a RNA virus capable of infecting humans and animals, has resulted in millions of deaths worldwide. Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infects the lungs, and the gastrointestinal tract to some extent. Rapid structural mutations have increased the virulence and infectivity of the virus drastically. One such mutated strain known as the UK variant has caused many deaths in the United Kingdom. HYPOTHESIS: Among several indigenous natural ingredients used for prevention and cure of many diseases, the catechins have been reported for their antiviral activity, even against SARS-CoV-2. Characteristic mutations present on the spike protein have presented the newer strain its enhanced infectivity. The spike protein helps the virus bind to ACE2 receptor of the host cell and hence is a drug target. Catechins have been reported for their entry-inhibitory activity against several viruses. METHOD: In this study, we performed molecular docking of different catechins with the wild and mutant variants of the spike protein of SARS-CoV-2. The stability of the best docked complexes was validated using molecular dynamics simulation. RESULTS: The in-silico studies show that the catechins form favourable interactions with the spike protein and can potentially impair its function. Epigallocatechin gallate (EGCG) showed the best binding among the catechins against both the strains. Both the protein-ligand complexes were stable throughout the simulation time frame. CONCLUSION: The outcomes should encourage further exploration of the antiviral activity of EGCG against SARS-CoV-2 and its variants.

The potential of BEN815 as an anti-inflammatory, antiviral and antioxidant agent for the treatment of COVID-19.

Background: The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective antiviral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough, it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal. Purpose: Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves (Psidium guajava), green tea leaves (Camellia sinensis), and rose petals (Rosa hybrida), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19. Study design: We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells. Methods: The principal active ingredients in BEN815 were determined and quantified using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining. Results: BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major constituents of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells. Conclusion: BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19.