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1.
Yakugaku Zasshi ; 140(10): 1251-1258, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999204

RESUMO

Natural materials such as crude drugs and foods are mixtures composed of various metabolites. Metabolic profiling is often used to identify possible correlations between a compound's metabolic profile and pharmacologic activity. Direct-injection electron ionization-mass spectrometry (DI-EI-MS) is a novel metabolomics method useful for characterizing biological materials. This review demonstrates the establishment of a DI-EI-MS method for metabolic profiling using several closely related lichen species: Cladonia krempelhuberi, C. gracilis, C. pseudogymnopoda, and C. ramulosa. The qualitative DI-EI-MS method was used to profile major and/or minor constituents in extracts of lichen samples. Each lichen sample could be distinguished by altering the DI-EI-MS electron energy and examining the resulting data using one-way analysis of variance. We also attempted to predict pharmacologic activity using DI-EI-MS metabolomics. Blueberry leaf extracts inhibited the proliferation of adult T-cell leukemia (ATL) cells. Blueberry leaf extracts could be distinguished by principal component analysis based on the absolute intensity of characteristic fragment ions. Twenty cultivars were categorized into four species, and the most appropriate discriminative marker m/z value for identifying each cultivar was selected statistically. Components extracted based on DI-EI-MS analyses could be used to construct a model to predict ATL cell bioactivity. These data suggest that the novel DI-EI-MS metabolomics method is suitable for identifying species of natural materials and predicting their pharmacologic activity. This approach could enhance public health by facilitating evaluations of pharmacologic activity and functionality, leading to the elimination of counterfeit products.


Assuntos
Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Mirtilos Azuis (Planta)/química , Mirtilos Azuis (Planta)/metabolismo , Líquens/metabolismo , Metabolômica , Extratos Vegetais/farmacologia , Proliferação de Células/efeitos dos fármacos , Previsões , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Espectrometria de Massas/métodos , Metabolômica/métodos , Extratos Vegetais/isolamento & purificação
2.
Signal Transduct Target Ther ; 5(1): 218, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-33011739

Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Glicosídeos Cardíacos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Animais , Antivirais/química , Betacoronavirus/patogenicidade , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Bufanolídeos/química , Bufanolídeos/farmacologia , Glicosídeos Cardíacos/química , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Cloroquina/química , Cloroquina/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Digoxina/química , Digoxina/farmacologia , Ensaios de Triagem em Larga Escala , Interações Hospedeiro-Patógeno/genética , Humanos , Janus Quinases/antagonistas & inibidores , Janus Quinases/genética , Janus Quinases/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Pandemias , Fenantrenos/química , Fenantrenos/farmacologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos
3.
Molecules ; 25(20)2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33050360

RESUMO

The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.


Assuntos
Betacoronavirus/isolamento & purificação , Produtos Biológicos/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Cisteína Endopeptidases/química , Pneumonia Viral/tratamento farmacológico , Polifenóis/farmacologia , Inibidores de Proteases/farmacologia , Serina Endopeptidases/química , Proteínas não Estruturais Virais/química , Antivirais/farmacologia , Simulação por Computador , Infecções por Coronavirus/virologia , Cisteína Endopeptidases/metabolismo , Humanos , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/virologia , Serina Endopeptidases/metabolismo , Proteínas não Estruturais Virais/metabolismo
4.
Molecules ; 25(18)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899754

RESUMO

The emergence of the Coronavirus Disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has led to an unprecedented pandemic, which demands urgent development of antiviral drugs and antibodies; as well as prophylactic approaches, namely vaccines. Algae biotechnology has much to offer in this scenario given the diversity of such organisms, which are a valuable source of antiviral and anti-inflammatory compounds that can also be used to produce vaccines and antibodies. Antivirals with possible activity against SARS-CoV-2 are summarized, based on previously reported activity against Coronaviruses or other enveloped or respiratory viruses. Moreover, the potential of algae-derived anti-inflammatory compounds to treat severe cases of COVID-19 is contemplated. The scenario of producing biopharmaceuticals in recombinant algae is presented and the cases of algae-made vaccines targeting viral diseases is highlighted as valuable references for the development of anti-SARS-CoV-2 vaccines. Successful cases in the production of functional antibodies are described. Perspectives on how specific algae species and genetic engineering techniques can be applied for the production of anti-viral compounds antibodies and vaccines against SARS-CoV-2 are provided.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Chlamydomonas reinhardtii/genética , Infecções por Coronavirus/tratamento farmacológico , Lectinas/farmacologia , Pneumonia Viral/tratamento farmacológico , Polifenóis/farmacologia , Polissacarídeos/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Núcleo Celular/química , Núcleo Celular/genética , Núcleo Celular/metabolismo , Chlamydomonas reinhardtii/química , Chlamydomonas reinhardtii/metabolismo , Cloroplastos/química , Cloroplastos/genética , Cloroplastos/metabolismo , Infecções por Coronavirus/prevenção & controle , Engenharia Genética/métodos , Humanos , Lectinas/química , Lectinas/isolamento & purificação , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Polifenóis/química , Polifenóis/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vacinas Virais/biossíntese , Vacinas Virais/farmacologia
5.
Molecules ; 25(17)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882868

RESUMO

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Produtos Biológicos/farmacologia , Infecções por Coronavirus/virologia , Flavonoides/farmacologia , Pneumonia Viral/virologia , Inibidores da Enzima Conversora de Angiotensina/química , Antivirais/química , Produtos Biológicos/química , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Suscetibilidade a Doenças , Flavonoides/química , Humanos , Estágios do Ciclo de Vida , Modelos Moleculares , Pandemias , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Vigilância da População , Relação Estrutura-Atividade
6.
Mar Drugs ; 18(10)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993146

RESUMO

For a long time, algal chemistry from terrestrial to marine or freshwater bodies, especially chlorophytes, has fascinated numerous investigators to develop new drugs in the nutraceutical and pharmaceutical industries. As such, chlorophytes comprise a diverse structural class of secondary metabolites, having functional groups that are specific to a particular source. All bioactive compounds of chlorophyte are of great interest due to their supplemental/nutritional/pharmacological activities. In this review, a detailed description of the chemical diversity of compounds encompassing alkaloids, terpenes, steroids, fatty acids and glycerides, their subclasses and their structures are discussed. These promising natural products have efficiency in developing new drugs necessary in the treatment of various deadly pathologies (cancer, HIV, SARS-CoV-2, several inflammations, etc.). Marine chlorophyte, therefore, is portrayed as a pivotal treasure in the case of drugs having marine provenience. It is a domain of research expected to probe novel pharmaceutically or nutraceutically important secondary metabolites resulting from marine Chlorophyta. In this regard, our review aims to compile the isolated secondary metabolites having diverse chemical structures from chlorophytes (like Caulerpa ssp., Ulva ssp., Tydemania ssp., Penicillus ssp., Codium ssp., Capsosiphon ssp., Avrainvillea ssp.), their biological properties, applications and possible mode of action.


Assuntos
Produtos Biológicos/farmacologia , Clorófitas/química , Clorófitas/metabolismo , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Produtos Biológicos/química , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Humanos , Neoplasias/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia
7.
Biochem Biophys Res Commun ; 530(1): 4-9, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828312

RESUMO

COVID-19 has become one of the worst epidemic in the world, currently already more than four million people have been infected, which probably co-exist with human beings, and has a significant impact on the global economy and political order. In the process of fighting against the epidemic in China, the clinical value of a variety of herbal medicines has been recognized and written into the clinical application guide. However, their effective molecular mechanism and potential targets are still not clear. Pathology and pharmacology research will gradually attract attention in the post-epidemic outbreak term. Here, we constructed a COVID-19 protein microarray of potential therapy targets, which contains the main drug targets to the SARS-CoV-2 virus and the anti-virus, anti-inflammatory cellar targets of the host. Series of quality controls test has been carried out, which showed that it could be applied for drug target screening of bio-active natural products. The establishment of this microarray will provide a useful tool for the study of the molecular pharmacology of natural products.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Pneumonia Viral/tratamento farmacológico , Proteínas/metabolismo , Proteínas Virais/metabolismo , Betacoronavirus/metabolismo , Produtos Biológicos/farmacologia , Ácido Clorogênico/farmacologia , Infecções por Coronavirus/metabolismo , Diterpenos/farmacologia , Descoberta de Drogas , Glucosídeos/farmacologia , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , Pandemias , Pneumonia Viral/metabolismo , Análise Serial de Proteínas , Estilbenos/farmacologia
8.
Molecules ; 25(16)2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32824454

RESUMO

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been the cause of a recent global pandemic. The highly contagious nature of this life-threatening virus makes it imperative to find therapies to counteract its diffusion. The main protease (Mpro) of SARS-CoV-2 is a promising drug target due to its indispensable role in viral replication inside the host. Using a combined two-steps approach of virtual screening and molecular docking techniques, we have screened an in-house collection of small molecules, mainly composed of natural and nature-inspired compounds. The molecules were selected with high structural diversity to cover a wide range of chemical space into the enzyme pockets. Virtual screening experiments were performed using the blind docking mode of the AutoDock Vina software. Virtual screening allowed the selection of structurally heterogeneous compounds capable of interacting effectively with the enzymatic site of SARS-CoV-2 Mpro. The compounds showing the best interaction with the protein were re-scored by molecular docking as implemented in AutoDock, while the stability of the complexes was tested by molecular dynamics. The most promising candidates revealed a good ability to fit into the protein binding pocket and to reach the catalytic dyad. There is a high probability that at least one of the selected scaffolds could be promising for further research.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Produtos Biológicos/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/farmacologia , Reposicionamento de Medicamentos , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Pandemias , Peptídeo Hidrolases/metabolismo , Proteínas da Matriz Viral/antagonistas & inibidores
9.
Chem Biol Interact ; 330: 109178, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738201

RESUMO

The capsaicin (vanilloid) receptor, TRPV1, is a heat-activated cation channel modulated by inflammatory mediators and contributes to acute and chronic pain. TRPV1 channel is one of the most researched and targeted mechanisms for the development of novel analgesics. Over the years, natural products have contributed enormously to the development of important therapeutic drugs used currently in modern medicine. A literature review was conducted using Medline, Google Scholar, and PubMed. Searching the literature resulted in listing 136 natural compounds that interacted with TRPV1 channel. These compounds were phytochemicals that belong to different chemical groups including vanilloids, flavonoids, alkaloids, terpenoids, terpenyl phenols, fatty acids, cannabinoids, sulfur_containing compounds, etc. Other natural TRPV1 modulators were of animal, fungal or bacterial origin. Some natural products were small agonists or antagonists of TRPV1. Others were protein venoms. Most in vitro studies utilized electrophysiological or calcium imaging techniques to study calcium flow through the channel using primary cultures of rat dorsal root and trigeminal ganglia. Other studies used hTRPV1 or rTRPV1 expressed in HEK239, CHO cells or Xenopus oocytes. In vivo studies concentrated on different pain models conducted mainly in mice and rats. In conclusion, natural products are highly diverse in their modulatory action on TRPV1. Many gaps in natural product research are present in distinguishing modality-specific from polymodal antagonists. Species' differences in TRPV1 functionality must be taken into account in any future study. Proceeding into clinical trials needs more efforts to discover potent TRPV1 antagonists devoid of hyperthermia, the main side effect.


Assuntos
Analgésicos/farmacologia , Produtos Biológicos/farmacologia , Canais de Cátion TRPV/metabolismo , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Animais , Produtos Biológicos/efeitos adversos , Cálcio/metabolismo , Técnicas de Cultura de Células , Febre/etiologia , Humanos , Dor/complicações , Dor/tratamento farmacológico , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/genética
10.
PLoS One ; 15(8): e0235723, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797045

RESUMO

Mixtures of drugs often have greater therapeutic value than any of their constituent drugs alone, and such combination therapies are widely used to treat diseases such as cancer, malaria, and viral infections. However, developing useful drug mixtures is challenging due to complex interactions between drugs. Natural substances can be fruitful sources of useful drug mixtures because secondary metabolites produced by living organisms do not often act in isolation in vivo. In order to facilitate the study of interactions within natural substances, a new analytical method to quantify interactions using data generated in the process of bioassay-guided fractionation is presented here: the extract fractional inhibitory concentration index (EFICI). The EFICI method uses the framework of Loewe additivity to calculate fractional inhibitory concentration values by which interactions can be determined for any combination of fractions that make up a parent extract. The EFICI method was applied to data on the bioassay-guided fractionation of Lechea mucronata and Schinus terebinthifolia for growth inhibition of the pathogenic bacterium Acinetobacter baumannii. The L. mucronata extract contained synergistic interactions (EFICI = 0.4181) and the S. terebinthifolia extract was non-interactive overall (EFICI = 0.9129). Quantifying interactions in the bioassay-guided fractionation of natural substances does not require additional experiments and can be useful to guide the experimental process and to support the development of standardized extracts as botanical drugs.


Assuntos
Antibacterianos/farmacologia , Produtos Biológicos/farmacologia , Extratos Vegetais/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Anacardiaceae/química , Antibacterianos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Fracionamento Químico , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos/métodos , Sinergismo Farmacológico , Humanos , Extratos Vegetais/isolamento & purificação
11.
Nutrients ; 12(9)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854262

RESUMO

The 2019 novel coronavirus, SARS-CoV-2, producing the disease COVID-19 is a pathogenic virus that targets mostly the human respiratory system and also other organs. SARS-CoV-2 is a new strain that has not been previously identified in humans, however there have been previous outbreaks of different versions of the beta coronavirus including severe acute respiratory syndrome (SARS-CoV1) from 2002 to 2003 and the most recent Middle East respiratory syndrome (MERS-CoV) which was first identified in 2012. All of the above have been recognised as major pathogens that are a great threat to public health and global economies. Currently, no specific treatment for SARS-CoV-2 infection has been identified; however, certain drugs have shown apparent efficacy in viral inhibition of the disease. Natural substances such as herbs and mushrooms have previously demonstrated both great antiviral and anti-inflammatory activity. Thus, the possibilities of natural substances as effective treatments against COVID-19 may seem promising. One of the potential candidates against the SARS-CoV-2 virus may be Inonotus obliquus (IO), also known as chaga mushroom. IO commonly grows in Asia, Europe and North America and is widely used as a raw material in various medical conditions. In this review, we have evaluated the most effective herbs and mushrooms, in terms of the antiviral and anti-inflammatory effects which have been assessed in laboratory conditions.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fungos/química , Magnoliopsida/química , Plantas Medicinais/química , Pneumonia Viral/tratamento farmacológico , Agaricales/química , Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Basidiomycota/química , Betacoronavirus , Produtos Biológicos/farmacologia , Chlorella/química , Infecções por Coronavirus/virologia , Humanos , Pandemias , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/virologia
12.
J Environ Pathol Toxicol Oncol ; 39(2): 159-177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749125

RESUMO

This review delineates the potential of naturally occurring substances for coronary artery disease (CAD), mainly coronary ischemia and its management, with their active constituents and probable mechanisms of action. As per the WHO, statistical incidence of CAD has increased in several countries. The number of coronary events worldwide has been increasing, and may increase even more in the near future. Meanwhile, increased sedentary behavior and poor diet will encourage the prevalence of CAD worldwide. As far as treatment is concerned, current conventional therapies have limitations due to their increased adverse events. The current approach to the management of CAD has certain lacunas that need to be overcome. Thus, new therapeutic options should be explored using traditional literature and current scientific data on natural products. The present review article deals with current knowledge associated with naturally occurring substances for the management of CAD.


Assuntos
Produtos Biológicos/farmacologia , Doença da Artéria Coronariana/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Medicina Herbária , Humanos
13.
Interdiscip Sci ; 12(3): 335-348, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32617855

RESUMO

Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Produtos Biológicos/farmacologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , RNA Replicase/antagonistas & inibidores , Proteínas não Estruturais Virais/antagonistas & inibidores , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/química , Alanina/farmacologia , Antivirais/química , Betacoronavirus/genética , Produtos Biológicos/química , Domínio Catalítico/genética , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Bases de Dados de Produtos Farmacêuticos , Avaliação Pré-Clínica de Medicamentos , Genoma Viral , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Humanos , Ligantes , Simulação de Acoplamento Molecular , Pandemias , Filogenia , Pneumonia Viral/epidemiologia , RNA Replicase/química , RNA Replicase/genética , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética
14.
Adv Exp Med Biol ; 1207: 709-724, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671788

RESUMO

Anti-cancer effect of natural products has been widely known. As a sort of multi-target anti-cancer agents, natural compound's regulation on autophagy in cancer cells has been studied as a promising research to reveal the mechanism in oncogenesis, as well as a potential short way to anti-cancer drug discovery. In this chapter, we reviewed the cancer-autophagic-related studies on several natural product compounds. It was concluded that natural product compounds directly or indirectly regulated most of the target proteins on the autophagic signal pathways. Considering we have not seen the whole clear atlas of autophagy in oncogenesis yet, it is hard to raise up any conclusion that autophagy is always playing a positive role in oncogenesis and cancer progression.


Assuntos
Autofagia , Produtos Biológicos/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
15.
Adv Exp Med Biol ; 1207: 725-730, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671789

RESUMO

Neurodegenerative diseases mainly include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD). It is now found that these diseases may be related to autophagic dysfunction. The mechanism is due to abnormalities in autophagy, which lead to abnormal or misfolded proteins accumulating in the cytoplasm, nucleus, and extracellular inclusion bodies, causing neuronal organelle damage and synaptic dysfunction. Since these diseases are much complex, the effect of monotherapy is not significantly affected. There is still a need to strengthen the study of anti-neurodegenerative drugs. Natural products should be a good source for the new drug discovery since most of natural products are multiple-target compounds. In this chapter, we reviewed some progress on studying resveratrol, curcumin, tripterine, and paeoniflorin. These natural products can eliminate abnormal protein aggregates by regulating autophagy, and thereby these compounds are promising to be used in prevention and treatment of neurodegenerative diseases in the future.


Assuntos
Autofagia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Doença de Alzheimer , Humanos , Doença de Huntington , Doenças Neurodegenerativas/prevenção & controle , Doença de Parkinson
16.
Adv Exp Med Biol ; 1207: 731-736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671790

RESUMO

Several major cardiovascular diseases, such as heart failure (HF) and atherosclerosis (AS), have been linked to autophagy dysfunction. The influence of autophagy on the occurrence and development of cardiovascular diseases has two sides. Generally, the induction of autophagy at a low level can provide energy and nutrients for cells through degradation of damaged organelles, protect cardiomyocytes and vascular endothelial cells, and stabilize atherosclerotic plaques. However, excessive autophagy may damage cardiomyocytes and vascular endothelial cells and even cause cell death. Therefore, the study on the role and mechanism of autophagy in the pathogenesis of cardiovascular diseases may not only provide new targets for the treatment of cardiac remodeling, myocardial ischemia and reperfusion injury, atherosclerosis and heart failure, but also provide clues for the developing new drugs on prevention and treatment of clinical cardiovascular diseases. In this chapter, we reviewed the research progress on resveratrol, curcumin, epigallocatechin-3-gallate, and cordyceps sinensis on their recent research progress for cardiovascular diseases. Regulating autophagy may be an effective strategy for the treatment of cardiovascular diseases in the future.


Assuntos
Autofagia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia
17.
Biomolecules ; 10(7)2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32645994

RESUMO

Oceans cover more than 70 percent of the surface of our planet and are characterized by huge taxonomic and chemical diversity of marine organisms. Several studies have shown that marine organisms produce a variety of compounds, derived from primary or secondary metabolism, which may have antiviral activities. In particular, certain marine metabolites are active towards a plethora of viruses. Multiple mechanisms of action have been found, as well as different targets. This review gives an overview of the marine-derived compounds discovered in the last 10 years. Even if marine organisms produce a wide variety of different compounds, there is only one compound available on the market, Ara-A, and only another one is in phase I clinical trials, named Griffithsin. The recent pandemic emergency caused by SARS-CoV-2, also known as COVID-19, highlights the need to further invest in this field, in order to shed light on marine compound potentiality and discover new drugs from the sea.


Assuntos
Antivirais/química , Organismos Aquáticos/química , Produtos Biológicos/química , Antivirais/farmacologia , Organismos Aquáticos/classificação , Produtos Biológicos/farmacologia , Coronaviridae/efeitos dos fármacos
18.
J Cancer Res Ther ; 16(3): 458-462, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719251

RESUMO

Background: Oral mucositis is a common and debilitating painful side effect of many forms of chemotherapy and radiation therapy. Mucositis may lead to dose reductions and unplanned interruptions of chemotherapy and/or radiotherapy (RT) and often affects patients' quality of life. Aim: The objective of the study was to assess the efficacy of the ayurvedic preparation in decreasing the severity of mucositis in head-and-neck cancer patients receiving concomitant chemoradiotherapy. Materials and Methods: In this prospective randomized study, the patients were divided into three groups. Group 1 patients received conventional mucositis treatment, whereas Group 2 patients received ayurvedic preparation Yashtimadhu in addition to conventional treatment. Group 3 patients received honey for local application in oral cavity as well as one tea spoon of honey twice daily orally in addition to routine conventional treatment. All the patients were assessed for mucositis at the end of every week during the RT for a period of 6 weeks. Results: A significant difference was observed between the groups at each time point. Nearly 42.85% of patients in conventional treatment arm developed Grade 3 mucositis, 20% of patients developed Grade 3 mucositis in group where honey was given, and only 15.5% of patients developed Grade 3 mucositis in Yastimadhu group. Unplanned treatment breaks and hospitalization of patients were reduced with the use of yashtimadhu as compared to other two groups. Conclusion: Yashtimadhu was observed to be effective and delayed the development of severe form of mucositis. The drug appeared to be more efficient in the management of radiation-induced mucositis.


Assuntos
Produtos Biológicos/farmacologia , Quimiorradioterapia/efeitos adversos , Glycyrrhiza/química , Neoplasias de Cabeça e Pescoço/radioterapia , Mucosa Bucal/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Estomatite/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/efeitos da radiação , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Estomatite/etiologia , Estomatite/patologia , Adulto Jovem
19.
Life Sci ; 258: 118129, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32717271

RESUMO

Ulcerative colitis (UC) is an inflammatory bowel disease with increasing incidence in the world, especially in developing countries. Although knowledge of its pathogenesis has progressed over the last years, some details require clarification. Studies have highlighted the role of microbial dysbiosis and immune dysfunction as essential factors that may initiate the typical high-grade inflammatory outcome. In order to better understand the immunopathophysiological aspects of UC, experimental murine models are valuable tools. Some of the most commonly used chemicals to induce colitis are trinitrobenzene sulfonic acid, oxazolone and dextran sodium sulfate. These may also be used to investigate new ways of preventing or treating UC and therefore improving targeting in human studies. The use of functional foods or bioactive compounds from plants may constitute an innovative direction towards the future of alternative medicine. Considering the above, this review focused on updated information regarding the 1. gut microbiota and immunopathogenesis of UC; 2. the most utilized animal models of the disease and their relevance; and 3. experimental application of natural products, not yet tested in clinical trials.


Assuntos
Produtos Biológicos/uso terapêutico , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Microbioma Gastrointestinal , Animais , Produtos Biológicos/farmacologia , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Modelos Biológicos
20.
Biochem Pharmacol ; 178: 114123, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32593613

RESUMO

Commonly used drugs for treating many conditions are either natural products or derivatives. In silico modelling has identified several natural products including quercetin as potential highly effective disruptors of the initial infection process involving binding to the interface between the SARS-CoV-2 (Covid-19) Viral Spike Protein and the epithelial cell Angiotensin Converting Enzyme-2 (ACE2) protein. Here we argue that the oral route of administration of quercetin is unlikely to be effective in clinical trials owing to biotransformation during digestion, absorption and metabolism, but suggest that agents could be administered directly by alternative routes such as a nasal or throat spray.


Assuntos
Betacoronavirus/efeitos dos fármacos , Produtos Biológicos/farmacologia , Peptidil Dipeptidase A/metabolismo , Quercetina/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Betacoronavirus/metabolismo , Betacoronavirus/fisiologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Ensaios Clínicos como Assunto/métodos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos/métodos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Estrutura Molecular , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Ligação Proteica/efeitos dos fármacos , Quercetina/administração & dosagem , Quercetina/química , Internalização do Vírus/efeitos dos fármacos
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