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1.
Int J Biol Sci ; 17(14): 3786-3794, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671199

RESUMO

COVID-19, caused by a novel coronavirus, SARS-CoV-2, poses a serious global threat. It was first reported in 2019 in China and has now dramatically spread across the world. It is crucial to develop therapeutics to mitigate severe disease and viral spread. The receptor-binding domains (RBDs) in the spike protein of SARS-CoV and MERS-CoV have shown anti-viral activity in previous reports suggesting that this domain has high potential for development as therapeutics. To evaluate the potential antiviral activity of recombinant SARS-CoV-2 RBD proteins, we determined the RBD residues of SARS-CoV-2 using a homology search with RBD of SARS-CoV. For efficient expression and purification, the signal peptide of spike protein was identified and used to generate constructs expressing recombinant RBD proteins. Highly purified RBD protein fused with the Fc domain of human IgG showed potent anti-viral efficacy, which was better than that of a protein fused with a histidine tag. Intranasally pre-administrated RBD protein also inhibited the attachment of SARS-COV-2 to mouse lungs. These findings indicate that RBD protein could be used for the prevention and treatment of SARS-CoV-2 infection.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/uso terapêutico , Ligação Viral/efeitos dos fármacos , Administração Intranasal , Sequência de Aminoácidos , Animais , Sítios de Ligação , Chlorocebus aethiops , Feminino , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Domínios Proteicos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Glicoproteína da Espícula de Coronavírus/biossíntese , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/farmacologia , Células Vero
2.
Enzyme Microb Technol ; 135: 109496, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146939

RESUMO

Catechins in green tea possess various health benefits. Enzymatic treatment improves physiological activities by inducing bioconversion of catechins. Here, we investigated the effect of green tea infusion (GT) after tannase treatment, which transforms (-)-epigallocatechin gallate (EGCG) to gallic acid (GA) and (-)-epigallocatechin (EGC), on adipocyte differentiation and mature adipocyte metabolism. The optimal conditions for tannase-mediated improvement in GA and EGC yields in GT were investigated using response surface methodology. Yields of GA and EGC were 43-fold (0.43 mg/mL) and 1.66-fold higher (1.11 mg/mL), respectively, compared to GT without tannase treatment. The optimal reaction conditions for tannase-mediated biotransformation were observed on 0.54 mg mL-1 of tannase, reaction time (86.79 min), and reaction temperature at 22.59 °C. GT and tannase-treated GT (TANs) upregulated adiponectin, uncoupling protein 1, adipose triglyceride lipase, and hormone-sensitive lipase gene expression in differentiated 3T3-L1 adipocytes, with TAN inducing better effects than GT, which implies that tannase treatment improved the beneficial effect of GT on adipocyte metabolism. Thus, tannase-mediated bio-transformation is an attractive candidate for preparing GT with enhanced anti-obesity properties.


Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Hidrolases de Éster Carboxílico/química , Catequina/análogos & derivados , Proteínas Fúngicas/química , Extratos Vegetais/química , Adipócitos/citologia , Adiponectina/genética , Adiponectina/metabolismo , Animais , Aspergillus/enzimologia , Biocatálise , Camellia sinensis/química , Catequina/química , Catequina/farmacologia , Diferenciação Celular , Manipulação de Alimentos , Ácido Gálico/química , Ácido Gálico/farmacologia , Camundongos , Células NIH 3T3 , Extratos Vegetais/farmacologia , Folhas de Planta/química , Chá/química , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
3.
Chem Biodivers ; 16(10): e1900347, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31532890

RESUMO

Catechins in green tea are well-known to be effective in reducing the risk of obesity. The purpose of this study was to elucidate the effects of catechins present in green tea on adipocyte differentiation and mature adipocyte metabolism. Treatment of 3T3-L1 mouse adipocyte during differentiation adipocytes with (-)-epigallocatechin (EGC) and gallic acid (GA) resulted in dose-dependent inhibition of adipogenesis. Specifically, EGC increased adiponectin and uncoupling protein 1 (UCP1) transcription in mature adipocytes. Transcription levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were not significantly impacted by either of the compounds. These results suggest that the EGC is the most effective catechin having anti-obesity activity. Finally, EGC is an attractive candidate component for remodeling obesity.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Catequina/análogos & derivados , Células 3T3-L1 , Tecido Adiposo Marrom/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Catequina/química , Catequina/isolamento & purificação , Catequina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Chá/química
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