The green tea catechin EGCG provides proof-of-concept for a pan-coronavirus attachment inhibitor DOI Creative Commons
Emmanuelle V. LeBlanc, Che C. Colpitts

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 28, 2022

Abstract The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emphasized serious threat to human health posed emerging coronaviruses. Effective broadly-acting antiviral countermeasures are urgently needed prepare for future CoVs, as vaccine development is not compatible with a rapid response newly virus. green tea catechin, epigallocatechin gallate (EGCG), broad-spectrum activity, although its mechanisms against coronavirus (CoV) infection have remained unclear. Here, we show that EGCG prevents and murine CoV blocks entry of lentiviral particles pseudotyped spike proteins from bat or highly pathogenic including SARS-CoV-2 variants concern, in lung epithelial cells. Mechanistically, treatment reduces attachment target cell surfaces interfering cell-surface glycans. Heparan sulfate proteoglycans required factor shown here be important endemic HCoV-OC43 infection. We can compete heparin, heparan analog, virion binding. Our results highlight conserved demonstrate potential pan-coronavirus inhibitors, which may useful protect CoVs.

Language: Английский

Screening of Poria cocos polysaccharide with immunomodulatory activity and its activation effects on TLR4/MD2/NF-κB pathway DOI

Mingjie Sun,

Liang Yao, Qimeng Yu

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 273, P. 132931 - 132931

Published: June 28, 2024

Language: Английский

Citations

13
Bioactive Molecules of Tea as Potential Inhibitors for RNA-Dependent RNA Polymerase of SARS-CoV-2 DOI Creative Commons
Vijay Kumar Bhardwaj, Rahul Singh, Jatin Sharma

et al.

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8

Published: May 31, 2021

The coronavirus disease (COVID-19), a worldwide pandemic, is caused by the severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). At this moment in time, there are no specific therapeutics available to combat COVID-19. Drug repurposing and identification of naturally bioactive molecules target SARS-CoV-2 among key strategies tackle notorious virus. enzyme RNA-dependent RNA polymerase (RdRp) performs pivotal role replicating RdRp prime for Remdesivir other nucleotides analog-based antiviral drugs. In study, we showed three from tea (epicatechin-3,5-di-O-gallate, epigallocatechin-3,5-di-O-gallate, epigallocatechin-3,4-di-O-gallate) that better interaction with critical residues present at catalytic center NTP entry channel than drugs Favipiravir. Our computational approach identify these included molecular docking studies, followed robust dynamics simulations. All readily could be made accessible along medications treat COVID-19 patients. However, results require validation further vitro vivo studies.

Language: Английский

Citations

55
An overview of potential inhibitors targeting non-structural proteins 3 (PLpro and Mac1) and 5 (3CLpro/Mpro) of SARS-CoV-2 DOI Creative Commons
Fangfang Yan, Feng Gao

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 4868 - 4883

Published: Jan. 1, 2021

There is an urgent need to develop effective treatments for coronavirus disease 2019 (COVID-19), which caused by severe acute respiratory syndrome 2 (SARS-CoV-2). The rapid spread of SARS-CoV-2 has resulted in a global pandemic that not only affected the daily lives individuals but also had significant impact on economy and public health. Although extensive research been conducted identify inhibitors targeting SARS-CoV-2, there are still no treatment strategies combat COVID-19. comprises two important proteolytic enzymes, namely, papain-like proteinase, located within non-structural protein 3 (nsp3), nsp5, both cleave large replicase polypeptides into multiple fragments required viral replication. Moreover, domain nsp3, known as macrodomain (Mac1), plays role Inhibition their functions should be able significantly interfere with replication cycle virus, therefore these key proteins may serve potential therapeutic targets. above targets corresponding have summarized current review. This review provides comprehensive updates nsp3 nsp5 inhibitor development would help advance discovery novel anti-viral therapeutics against SARS-CoV-2.

Language: Английский

Citations

49
Epigallocatechin Gallate (EGCG), a Green Tea Polyphenol, Reduces Coronavirus Replication in a Mouse Model DOI Creative Commons
Rackhyun Park, Minsu Jang, Yea‐In Park

et al.

Viruses, Journal Year: 2021, Volume and Issue: 13(12), P. 2533 - 2533

Published: Dec. 17, 2021

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 replication vitro. Herein, we examined the inhibitory effect polyphenols on mouse model. We used epigallocatechin gallate (EGCG) and containing more than 60% catechin (GTP60) human OC43 (HCoV-OC43) surrogate for SARS-CoV-2. Scanning electron microscopy analysis results showed HCoV-OC43 infection virion particle production infected cells. EGCG GTP60 treatment reduced protein virus Finally, EGCG- GTP60-fed mice exhibited levels RNA lungs. These demonstrate polyphenol is decreasing level vivo.

Language: Английский

Citations

41
Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity DOI Open Access
Mohamed Haddad, Roger Gaudreault, Gabriel Sasseville

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2643 - 2643

Published: Feb. 27, 2022

The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. identification small natural ligands that could prevent the entry and/or replication remains a pertinent approach to fight disease (COVID-19) pandemic. Previously, we showed phenolic compounds corilagin and 1,3,6-tri-O-galloyl-β-D-glucose (TGG) inhibit interaction between SARS-CoV-2 spike protein receptor binding domain (RBD) angiotensin-converting enzyme (ACE2), target cell membrane host organism. Building these promising results, now assess effects two other crucial targets involved in replication, respectively: transmembrane protease serine (TMPRSS2) 3-chymotrypsin like (3CLpro) inhibitors. Since corilagin, TGG, tannic acid (TA) share many physicochemical structural properties, investigate TA targets. In this work, combination experimental methods (biochemical inhibition assays, surface plasmon resonance, quartz crystal microbalance with dissipation monitoring) confirms potential role prevention infectivity through extracellular RBD/ACE2 interactions TMPRSS2 3CLpro activity. Moreover, molecular docking prediction followed by dynamic simulation mechanics Poisson-Boltzmann area (MMPBSA) free energy calculation also shows binds RBD, TMPRSS2, higher affinities than TGG corilagin. Overall, results suggest naturally occurring candidate SARS-CoV-2.

Language: Английский

Citations

34
Role of Ajwa Date Fruit Pulp and Seed in the Management of Diseases through In Vitro and In Silico Analysis DOI Creative Commons
Shehwaz Anwar, Ravindra Raut, Mohammed A. Alsahli

et al.

Biology, Journal Year: 2022, Volume and Issue: 11(1), P. 78 - 78

Published: Jan. 5, 2022

This study investigated the health-promoting activities of methanolic extracts Ajwa date seed and fruit pulp through in vitro studies. These studies confirmed potential antioxidant, anti-hemolytic, anti-proteolytic, anti-bacterial associated with dates. The EC50 values methanol were reported to be 1580.35 ± 0.37 1272.68 0.27 µg/mL, respectively, DPPH test. maximum percentage hydrogen peroxide-reducing activity was 71.3 65.38% for both at 600 µg/mL. Fruit inhibited heat-induced BSA denaturation by 68.11 60.308%, hemolysis 63.84% 58.10%, hypersalinity-induced 61.71% 57.27%, showed anti-proteinase 56.8 51.31% μg/mL, respectively. Seed egg albumin same concentration 44.31 50.84%, minimum browning intensity 63.2%, percent aggregation index 64.2%, amyloid structure 63.8% μg/mL. At 100 mg/mL, extract exhibited good antibacterial activity. Molecular docking analysis that ten active constituents seeds bind critical antioxidant enzymes, catalase (1DGH) superoxide dismutase (5YTU). functional residues involved such interactions include Arg72, Ala357, Leu144 1DGH, Gly37, Pro13, Asp11 5YTU. Hence, dates can used develop a suitable alternative therapy various diseases, including diabetes possibly COVID-19-associated complications.

Language: Английский

Citations

30
A VSV-based assay quantifies coronavirus Mpro/3CLpro/Nsp5 main protease activity and chemical inhibition DOI Creative Commons
Emmanuel Heilmann, Francesco Costacurta, Stephan Geley

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: April 27, 2022

Abstract Protease inhibitors are among the most powerful antiviral drugs. However, for SARS-CoV-2 only a small number of protease have been identified thus far and there is still great need assays that efficiently report activity inhibition in living cells. Here, we engineer safe VSV-based system to both gain- loss-of-function coronavirus main (M pro /3CLpro/Nsp5) We use 3CLpro this confirm susceptibility known (boceprevir, GC376, PF-00835231, PF-07321332/nirmatrelvir) reevaluate other reported (baicalein, ebselen, carmofur, ethacridine, ivermectin, masitinib, darunavir, atazanavir). Moreover, show can be adapted function chemical proteases from different species as well distantly related viruses. Together with fact live cell also reflect compound permeability toxicity, anticipate will useful identification optimization additional inhibitors.

Language: Английский

Citations

30
Multispectroscopic and computational simulation insights into the inhibition mechanism of epigallocatechin-3-gallate on polyphenol oxidase DOI
Xuezhi Tian, Lei Rao, Liang Zhao

et al.

Food Chemistry, Journal Year: 2022, Volume and Issue: 393, P. 133415 - 133415

Published: June 6, 2022

Language: Английский

Citations

29
Network pharmacology based research into the effect and potential mechanism of Portulaca oleracea L. polysaccharide against ulcerative colitis DOI
Yang Yang, Xiechen Zhou, Guiyan Jia

et al.

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 161, P. 106999 - 106999

Published: May 12, 2023

Language: Английский

Citations

22
Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19 DOI Creative Commons
Nadine Krüger, Thales Kronenberger, Hang Xie

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 190 - 190

Published: Jan. 28, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to disease 2019 (COVID-19) pandemic. main protease SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from viral RNA, making it validated target for therapeutics. New chemical phenotypes are frequently discovered in natural goods. In current study, we used fluorogenic assay test variety products their ability inhibit Mpro. Several compounds were Mpro at low micromolar concentrations. It was possible crystallize robinetin together with Mpro, and X-ray structure revealed covalent interaction protease's catalytic Cys145 site. Selected potent molecules also exhibited properties without cytotoxicity. Some these powerful inhibitors might be utilized as lead future COVID-19 research.

Language: Английский

Citations

18