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1.
Viruses ; 13(12)2021 12 17.
Article in English | MEDLINE | ID: covidwho-1580427

ABSTRACT

The COVID-19 pandemic has resulted in a huge number of deaths from 2020 to 2021; however, effective antiviral drugs against SARS-CoV-2 are currently under development. Recent studies have demonstrated that green tea polyphenols, particularly EGCG, inhibit coronavirus enzymes as well as coronavirus replication in vitro. Herein, we examined the inhibitory effect of green tea polyphenols on coronavirus replication in a mouse model. We used epigallocatechin gallate (EGCG) and green tea polyphenols containing more than 60% catechin (GTP60) and human coronavirus OC43 (HCoV-OC43) as a surrogate for SARS-CoV-2. Scanning electron microscopy analysis results showed that HCoV-OC43 infection resulted in virion particle production in infected cells. EGCG and GTP60 treatment reduced coronavirus protein and virus production in the cells. Finally, EGCG- and GTP60-fed mice exhibited reduced levels of coronavirus RNA in mouse lungs. These results demonstrate that green tea polyphenol treatment is effective in decreasing the level of coronavirus in vivo.


Subject(s)
Antiviral Agents/pharmacology , Catechin/analogs & derivatives , Coronavirus Infections/drug therapy , Polyphenols/pharmacology , Tea/chemistry , Virus Replication/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Catechin/pharmacology , Catechin/therapeutic use , Cell Line , Coronavirus Infections/virology , Coronavirus OC43, Human/drug effects , Coronavirus OC43, Human/physiology , Disease Models, Animal , Humans , Mice , Polyphenols/chemistry , Polyphenols/therapeutic use
2.
Molecules ; 26(19)2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1444276

ABSTRACT

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5-46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.


Subject(s)
Acute Kidney Injury/etiology , Antiviral Agents/pharmacology , COVID-19/complications , Catechin/pharmacology , Protective Agents/pharmacology , Acute Kidney Injury/drug therapy , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Catechin/chemistry , Catechin/therapeutic use , Humans , Protective Agents/chemistry , Protective Agents/therapeutic use , SARS-CoV-2/drug effects
3.
Brief Bioinform ; 22(2): 1346-1360, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343647

ABSTRACT

The global pandemic crisis, coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines have not turned to be realistic within the timeframe needed to combat this pandemic. Here, we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, whichare crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 75 FDA-approved potential antiviral drugs against the target proteins, spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), cathepsin L (CTSL), nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and non-structural protein 6 (NSP6), resulted in the selection of seven drugs which preferentially bind to the target proteins. Further, the molecular interactions determined by molecular dynamics simulation revealed that among the 75 drug molecules, catechin can effectively bind to 3CLpro, CTSL, RBD of S protein, NSP6 and nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol (CTSL) to -26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values: -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favorable molecular interaction of catechin toward multiple target proteins signify that catechin can be potentially explored as a multi-targeted agent against COVID-19.


Subject(s)
COVID-19/drug therapy , Catechin/pharmacology , Polyphenols/pharmacology , SARS-CoV-2/drug effects , COVID-19/virology , Catechin/chemistry , Catechin/therapeutic use , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Polyphenols/therapeutic use
4.
Molecules ; 26(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1304690

ABSTRACT

Influenza is one of the most serious respiratory viral infections worldwide. Although several studies have reported that green tea catechins (GTCs) might prevent influenza virus infection, this remains controversial. We performed a systematic review and meta-analysis of eight studies with 5,048 participants that examined the effect of GTC administration on influenza prevention. In a random-effects meta-analysis of five RCTs, 884 participants treated with GTCs showed statistically significant effects on the prevention of influenza infection compared to the control group (risk ratio (RR) 0.67, 95%CIs 0.51-0.89, P = 0.005) without evidence of heterogeneity (I2= 0%, P = 0.629). Similarly, in three cohort studies with 2,223 participants treated with GTCs, there were also statistically significant effects (RR 0.52, 95%CIs 0.35-0.77, P = 0.001) with very low evidence of heterogeneity (I2 = 3%, P = 0.358). Additionally, the overall effect in the subgroup analysis of gargling and orally ingested items (taking capsules and drinking) showed a pooled RR of 0.62 (95% CIs 0.49-0.77, P = 0.003) without heterogeneity (I2= 0%, P = 0.554). There were no obvious publication biases (Egger's test (P = 0.138) and Begg's test (P = 0.103)). Our analysis suggests that green tea consumption is effective in the prophylaxis of influenza infections. To confirm the findings before implementation, longitudinal clinical trials with specific doses of green tea consumption are warranted.


Subject(s)
Antiviral Agents/therapeutic use , Catechin/therapeutic use , Plant Extracts/chemistry , Tea/chemistry , Antiviral Agents/chemistry , Catechin/chemistry , Clinical Trials as Topic , Humans , Influenza, Human
5.
Molecules ; 26(13)2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1288963

ABSTRACT

(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were also discussed.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Catechin/analogs & derivatives , Tea/chemistry , Animals , Antiviral Agents/therapeutic use , Catechin/pharmacology , Catechin/therapeutic use , Humans , Virus Internalization/drug effects , Viruses/drug effects
7.
Molecules ; 26(5)2021 Feb 24.
Article in English | MEDLINE | ID: covidwho-1100140

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged to be the greatest threat to humanity in the modern world and has claimed nearly 2.2 million lives worldwide. The United States alone accounts for more than one fourth of 100 million COVID-19 cases across the globe. Although vaccination against SARS-CoV-2 has begun, its efficacy in preventing a new or repeat COVID-19 infection in immunized individuals is yet to be determined. Calls for repurposing of existing, approved, drugs that target the inflammatory condition in COVID-19 are growing. Our initial gene ontology analysis predicts a similarity between SARS-CoV-2 induced inflammatory and immune dysregulation and the pathophysiology of rheumatoid arthritis. Interestingly, many of the drugs related to rheumatoid arthritis have been found to be lifesaving and contribute to lower COVID-19 morbidity. We also performed in silico investigation of binding of epigallocatechin gallate (EGCG), a well-known catechin, and other catechins on viral proteins and identified papain-like protease protein (PLPro) as a binding partner. Catechins bind to the S1 ubiquitin-binding site of PLPro, which might inhibit its protease function and abrogate SARS-CoV-2 inhibitory function on ubiquitin proteasome system and interferon stimulated gene system. In the realms of addressing inflammation and how to effectively target SARS-CoV-2 mediated respiratory distress syndrome, we review in this article the available knowledge on the strategic placement of EGCG in curbing inflammatory signals and how it may serve as a broad spectrum therapeutic in asymptomatic and symptomatic COVID-19 patients.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , Catechin/analogs & derivatives , Coronavirus 3C Proteases , Cysteine Proteinase Inhibitors , SARS-CoV-2/enzymology , Tea/chemistry , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Binding Sites , COVID-19/enzymology , COVID-19/epidemiology , Catechin/chemistry , Catechin/therapeutic use , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Cysteine Proteinase Inhibitors/chemistry , Cysteine Proteinase Inhibitors/therapeutic use , Humans
8.
Biochemistry (Mosc) ; 85(7): 833-837, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-772260

ABSTRACT

Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Molecular Targeted Therapy/methods , NF-E2-Related Factor 2/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , COVID-19 , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/therapeutic use , Coronavirus Infections/virology , Dimethyl Fumarate/pharmacology , Dimethyl Fumarate/therapeutic use , Female , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Inflammation/metabolism , Isothiocyanates/pharmacology , Isothiocyanates/therapeutic use , Male , Mice , Oxidative Stress/drug effects , Pandemics , Pneumonia, Viral/virology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/virology , Resveratrol/pharmacology , Resveratrol/therapeutic use , SARS-CoV-2 , Signal Transduction/drug effects , Sulfoxides , Thiosulfates/pharmacology , Thiosulfates/therapeutic use
9.
Int J Mol Sci ; 21(14)2020 Jul 21.
Article in English | MEDLINE | ID: covidwho-671084

ABSTRACT

Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Catechin/analogs & derivatives , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Pneumonia, Viral/drug therapy , Antioxidants/therapeutic use , Autoimmune Diseases/drug therapy , Betacoronavirus/drug effects , Betacoronavirus/immunology , COVID-19 , Catechin/therapeutic use , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/pathology , Humans , NF-kappa B/antagonists & inhibitors , Pandemics , Plant Extracts/therapeutic use , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/prevention & control , SARS-CoV-2 , STAT1 Transcription Factor/antagonists & inhibitors , STAT3 Transcription Factor/antagonists & inhibitors , Signal Transduction/drug effects
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