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1.
Curr Protein Pept Sci ; 25(4): 307-325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38265408

RESUMO

The global pandemic caused by COVID-19 posed a significant challenge to public health, necessitating rapid scientific interventions to tackle the spread of infection. The review discusses the key areas of research on COVID-19 including viral genomics, epidemiology, pathogenesis, diagnostics, and therapeutics. The genome sequencing of the virus facilitated the tracking of its evolution, transmission dynamics, and identification of variants. Epidemiological studies have provided insights into disease spread, risk factors, and the impact of public health infrastructure and social distancing measures. Investigations of the viral pathogenesis have elucidated the mechanisms underlying immune responses and severe manifestations including the long-term effects of COVID-19. Overall, the article provides an updated overview of the diagnostic methods developed for SARS-CoV-2 and discusses their strengths, limitations, and appropriate utilization in different clinical and public health settings. Furthermore, therapeutic approaches including antiviral drugs, immunomodulatory therapies, and repurposed medications have been investigated to alleviate disease severity and improve patient outcomes. Through a comprehensive analysis of these scientific efforts, the review provides an overview of the advancements made in understanding and tackling SARS-CoV-2, while underscoring the need for continued research to address the evolving challenges posed by this global health crisis.


Assuntos
Antivirais , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/virologia , COVID-19/epidemiologia , COVID-19/transmissão , SARS-CoV-2/genética , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Antivirais/uso terapêutico , Pandemias/prevenção & controle , Genoma Viral , Saúde Global , Tratamento Farmacológico da COVID-19
2.
Protein Pept Lett ; 30(7): 541-551, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37211849

RESUMO

Designing effective diagnostics, biotherapeutics, and biocatalysts are a few interesting potential outcomes of protein engineering. Despite being just a few decades old, the discipline of de novo protein designing has provided a foundation for remarkable outcomes in the pharmaceuticals and enzyme industries. The technologies that will have the biggest impact on current protein therapeutics include engineered natural protein variants, Fc fusion protein, and antibody engineering. Furthermore, designing protein scaffolds can be used in developing next-generation antibodies and in transplanting active sites in the enzyme. The article highlights the important tools and techniques used in protein engineering and their application in the engineering of enzymes and therapeutic proteins. This review further sheds light on the engineering of superoxide dismutase, an enzyme responsible for catalyzing the conversion of superoxide radicals to oxygen and hydrogen peroxide by catalyzing a redox reaction at the metal center while concurrently oxidizing and reducing superoxide free radicals.


Assuntos
Engenharia de Proteínas , Proteínas , Proteínas/química , Engenharia de Proteínas/métodos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Anticorpos/metabolismo , Oxirredução
3.
Front Mol Biosci ; 10: 1104577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825200

RESUMO

The most severe clinical manifestations of the horrifying COVID-19 disease, that claimed millions of lives during the pandemic time, were Acute respiratory distress syndrome (ARDS), Coagulopathies, septic shock leading eventually to death. ARDS was a consequence of Cytokine storm. The viral SARS-COV2infection lead to avalanche of cytokines and eicosanoids causing "cytokine storm" and "eicosanoid storm." Cytokine storm is one of the macrophage-derived inflammatory responses triggered by binding of virus particles to ACE2 receptors of alveolar macrophages, arise mainly due to over production of various pro-inflammatory mediators like cytokines, e.g., interleukin (IL)-1, IL-2, and tumor necrosis factor (TNF)- α, causing pulmonary edema, acute respiratory distress, and multi-organ failure. Cytokine storm was regarded as the predictor of severity of the disease and was deemed one of the causes of the high mortality rates due to the COVID-19. The basis of cytokine storm is imbalanced switching between an inflammation increasing - pro-inflammatory (M1) and an inflammation regulating-anti-inflammatory (M2) forms of alveolar macrophages which further deteriorates if opportunistic secondary bacterial infections prevail in the lungs. Lack of sufficient knowledge regarding the virus and its influence on co-morbidities, clinical treatment of the diseases included exorbitant use of antibiotics to mitigate secondary bacterial infections, which led to the unwarranted development of multidrug resistance (MDR) among the population across the globe. Antimicrobial resistance (AMR) needs to be addressed from various perspectives as it may deprive future generations of the basic health immunity. Specialized pro-resolving mediators (SPMs) are generated from the stereoselective enzymatic conversions of essential fatty acids that serve as immune resolvents in controlling acute inflammatory responses. SPMs facilitate the clearance of injured tissue and cell debris, the removal of pathogens, and augment the concentration of anti-inflammatory lipid mediators. The SPMs, e.g., lipoxins, protectins, and resolvins have been implicated in exerting inhibitory influence on with cytokine storm. Experimental evidence suggests that SPMS lower antibiotic requirement. Therefore, in this review potential roles of SPMs in enhancing macrophage polarization, triggering immunological functions, hastening inflammation resolution, subsiding cytokine storm and decreasing antibiotic requirement that can reduce AMR load are discussed.

4.
Curr Protein Pept Sci ; 24(1): 7-21, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36366847

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously present in the environment. These compounds have demonstrated both mutagenic and carcinogenic properties. In the past few decades, scientists have constantly been looking for a possible route to their biological degradation. Bacterial ring hydroxylating dioxygenases (RHDs) implicated in the polycyclic aromatic hydrocarbon degradation comprise a large family of enzymes. RHD catalyzes the stereospecific oxidation of PAHs by incorporating molecular oxygen into inert aromatic nuclei. These biocatalysts hold the potential to completely transform and mineralize toxic forms of these compounds into non-toxic forms. RHDsmediated oxygenation produces cis-dihydrodiols, a chiral compound used in pharmaceutical industries. The Molecular investigation of 16S rRNA and key functional genes involved in pollutant degradation have revealed the dominant occurrence of phylum proteobacteria and actinobacteria in hydrocarbonpolluted environments. The present review is aimed at narrating the diversity, distribution, structural and functional characteristics of RHDs. The review further highlights key amino acids participating in RHDs catalysis. It also discusses the robustness of protein engineering methods in improving the structural and functional activity of the ring hydroxylating dioxygenases.


Assuntos
Dioxigenases , Hidrocarbonetos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos , Dioxigenases/genética , Dioxigenases/metabolismo , RNA Ribossômico 16S/genética , Hidrocarbonetos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Bactérias , Biodegradação Ambiental
5.
Curr Protein Pept Sci ; 23(9): 574-584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082852

RESUMO

The major drawbacks of biofuel production at the commercial level are its low yield, nonavailability of feedstock, feedback inhibition, presence of inhibitory pathways in various organisms, and biofuel intolerance of organisms. The present review focuses on the implications of the CRISPRCas9 mediated gene editing tool to alter the genome of bacteria, algae, fungi, and higher plants for efficient biofuel production. Gene knockout and gene cassette insertions employing CRISPR-Cas9 in Saccharomyces cerevisiae and Kluyveromyces marxianus have resulted in enhanced production of bioethanol and 2-Phenyl ethanol in these organisms, respectively. Genomes of several bacterial strains were also modified to enhance ethanol and butanol production in them. CRISPR-Cas9 modification of microalgae has demonstrated improved total lipid content, a prerequisite for biofuel production. All over, CRISPR-Cas9 has emerged as a tool of choice for engineering the genome and metabolic pathways of organisms for producing industrial biofuel. In plant-based biofuel production, the biosynthetic pathways of lignin interfere with the satisfactory release of fermentable sugars thus hampering efficient biofuel production. CRISPR-Cas9 has shown a promising role in reducing lignin content in various plants including barley, switchgrass, and rice straw.


Assuntos
Biocombustíveis , Sistemas CRISPR-Cas , Lignina/metabolismo , Edição de Genes/métodos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Etanol/metabolismo
6.
Microbiol Res ; 265: 127206, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36162150

RESUMO

COVID-19 (Coronavirus Disease 2019), a life-threatening viral infection, is caused by a highly pathogenic virus named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Currently, no treatment is available for COVID-19; hence there is an urgent need to find effective therapeutic drugs to combat COVID-19 pandemic. Considering the fact that the world is facing a major issue of antimicrobial drug resistance, naturally occurring compounds have the potential to achieve this goal. Antimicrobial peptides (AMPs) are naturally occurring antimicrobial agents which are effective against a wide variety of microbial infections. Therefore, the use of AMPs is an attractive therapeutic strategy for the treatment of SARS-CoV-2 infection. This review sheds light on the potential of antimicrobial peptides as antiviral agents followed by a comprehensive description of effective antiviral peptides derived from various natural sources found to be effective against SARS-CoV and other respiratory viruses. It also highlights the mechanisms of action of antiviral peptides with special emphasis on their effectiveness against SARS-CoV-2 infection.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Peptídeos Antimicrobianos , Antivirais/farmacologia , Resistência a Múltiplos Medicamentos , Humanos , Pandemias
7.
Artigo em Inglês | MEDLINE | ID: mdl-35388304

RESUMO

The incidence of obesity and over bodyweight is emerging as a major health concern. Obesity is a complex metabolic disease with multiple pathophysiological clinical conditions as comorbidities are associated with obesity such as diabetes, hypertension, cardiovascular disorders, sleep apnea, osteoarthritis, some cancers, and inflammation-based clinical conditions. In obese individuals, adipocyte cells increased the expression of leptin, angiotensin, adipocytokines, plasminogen activators, and C-reactive protein. Currently, options for treatment and lifestyle behaviors interventions are limited, and keeping a healthy lifestyle is challenging. Various types of phytochemicals have been investigated for antiobesity potential. Here, we discuss pathophysiology and signaling pathways in obesity, epigenetic regulations, regulatory mechanism, functional ingredients in natural antiobesity products, and therapeutic application of phytochemicals in obesity.

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