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1.
Front Immunol ; 12: 660298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093548

RESUMO

In addition to SARS-CoV-2 and its variants, emerging viruses that cause respiratory viral infections will continue to arise. Increasing evidence suggests a delayed, possibly suppressed, type 1 interferon (IFN-I) response occurs early during COVID-19 and other viral respiratory infections such as SARS and MERS. These observations prompt considering IFN-ß as a prophylactic or early intervention for respiratory viral infections. A rationale for developing and testing intranasal interferon beta (IFN-ß) as an immediately available intervention for new respiratory viral infections that will arise unexpectedly in the future is presented and supported by basic and clinical trial observations. IFN-ß prophylaxis could limit the spread and consequences of an emerging respiratory viral infection in at-risk individuals while specific vaccines are being developed.


Assuntos
Interferon Tipo I/administração & dosagem , Profilaxia Pré-Exposição , Infecções Respiratórias/prevenção & controle , Viroses/prevenção & controle , Administração Intranasal , Humanos , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Índice de Gravidade de Doença , Viroses/tratamento farmacológico , Viroses/imunologia
2.
Cells ; 10(5)2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066434

RESUMO

Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5'-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid ß-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antivirais/farmacologia , Transdução de Sinais/imunologia , Viroses/imunologia , Antivirais/uso terapêutico , Autofagia/efeitos dos fármacos , Autofagia/imunologia , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/imunologia , Proliferação de Células/efeitos dos fármacos , Desenvolvimento de Medicamentos , Humanos , Pandemias/prevenção & controle , SARS-CoV-2/imunologia , Transdução de Sinais/efeitos dos fármacos , Viroses/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
3.
Cells ; 10(5)2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064516

RESUMO

Sphingolipids are important structural membrane components and, together with cholesterol, are often organized in lipid rafts, where they act as signaling molecules in many cellular functions. They play crucial roles in regulating pathobiological processes, such as cancer, inflammation, and infectious diseases. The bioactive metabolites ceramide, sphingosine-1-phosphate, and sphingosine have been shown to be involved in the pathogenesis of several microbes. In contrast to ceramide, which often promotes bacterial and viral infections (for instance, by mediating adhesion and internalization), sphingosine, which is released from ceramide by the activity of ceramidases, kills many bacterial, viral, and fungal pathogens. In particular, sphingosine is an important natural component of the defense against bacterial pathogens in the respiratory tract. Pathologically reduced sphingosine levels in cystic fibrosis airway epithelial cells are normalized by inhalation of sphingosine, and coating plastic implants with sphingosine prevents bacterial infections. Pretreatment of cells with exogenous sphingosine also prevents the viral spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from interacting with host cell receptors and inhibits the propagation of herpes simplex virus type 1 (HSV-1) in macrophages. Recent examinations reveal that the bactericidal effect of sphingosine might be due to bacterial membrane permeabilization and the subsequent death of the bacteria.


Assuntos
Infecções Bacterianas/imunologia , Micoses/imunologia , Transdução de Sinais/imunologia , Esfingosina/metabolismo , Viroses/imunologia , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Parede Celular/efeitos dos fármacos , Ceramidas/metabolismo , Modelos Animais de Doenças , Herpesvirus Humano 1/imunologia , Humanos , Lisofosfolipídeos/metabolismo , Microdomínios da Membrana/imunologia , Microdomínios da Membrana/metabolismo , Micoses/tratamento farmacológico , Micoses/metabolismo , Micoses/microbiologia , SARS-CoV-2/imunologia , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Esfingosina/uso terapêutico , Viroses/tratamento farmacológico , Viroses/metabolismo , Viroses/virologia
4.
BMC Infect Dis ; 21(1): 509, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059003

RESUMO

BACKGROUND: Readily-available diagnostics do not reliably discriminate between viral and bacterial pediatric uncomplicated pneumonia, both of which are common. Some have suggested that assessment of pneumococcal carriage could be used to identify those children with bacterial pneumonia. The objective of this study was to determine if nasopharyngeal pneumococcal colonization patterns differed between children with definite viral disease, definite bacterial disease, and respiratory disease of indeterminate etiology. METHODS: Three groups of subjects were recruited: children with critical respiratory illness, previously healthy children with respiratory illness admitted to the ward, and previously healthy children diagnosed in the emergency department with non-severe pneumonia. Subjects were categorized as follows: a) viral infection syndrome (eg. bronchiolitis), b) bacterial infection syndrome (ie. pneumonia complicated by effusion/empyema), or c) 'indeterminate' pneumonia. Subjects' nasopharyngeal swabs underwent quantitative PCR testing for S. pneumoniae. Associations between categorical variables were determined with Fisher's exact, chi-square, or logistic regression, as appropriate. Associations between quantitative genomic load and categorical variables was determined by linear regression. RESULTS: There were 206 children in Group 1, 122 children in Group 2, and 179 children in Group 3. Only a minority (227/507, 45%) had detectable pneumococcal carriage; in those subjects, there was no association of quantitative genomic load with age, recruitment group, or disease category. In multivariate logistic regression, pneumococcal colonization > 3 log copies/mL was associated with younger age and recruitment group, but not with disease category. CONCLUSIONS: The nasopharyngeal S. pneumoniae colonization patterns of subjects with definite viral infection were very similar to colonization patterns of those with definite bacterial infection or indeterminate pneumonia. Assessment and quantification of nasopharyngeal pneumococcal colonization does not therefore appear useful to discriminate between acute viral and bacterial respiratory disease; consequently, this diagnostic testing is unlikely to reliably determine which children with indeterminate pneumonia have a bacterial etiology and/or require antibiotic treatment.


Assuntos
Nasofaringe/microbiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Canadá/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Contagem de Colônia Microbiana , Estudos Transversais , Humanos , Lactente , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Streptococcus pneumoniae/genética , Viroses/diagnóstico , Viroses/tratamento farmacológico , Viroses/epidemiologia
5.
Virologie (Montrouge) ; 25(2): 63-92, 2021 04 01.
Artigo em Francês | MEDLINE | ID: mdl-33973852

RESUMO

Epigenetics play an important role in viral replication and in viral associated pathogenesis. In fact, viruses interact with epigenetic factors to promote the viral replication by stimulating the entry into the lytic cycle, but also by promoting viral latency. Furthermore, epigenetics control the immune response implemented by the host to counteract viral infections. Thus, epigenetic modifications are identified as potential therapeutic targets to control viral infections. Several studies have already shown the efficiency of inhibitors of histone deacetylases, demethylases, acetyltransferases and methyltransferases, as well as inhibitors of DNA methyltransferases in viral infections repression or in latency reactivation. In this review, we will examine the epigenetic regulation of viral infections by several DNA viruses, e.g. HSV, EBV, HCMV, KSHV, HBV, HPV and HAdV, and RNA viruses, e.g. HCV, HIV, IAV and CoV. Also, we will discuss the potential use of therapeutic approaches targeting epigenetics for the control of viral infections.


Assuntos
Herpesvirus Humano 8 , Viroses , Epigênese Genética , Humanos , Viroses/tratamento farmacológico , Viroses/genética , Latência Viral , Replicação Viral/genética
6.
Front Immunol ; 12: 637553, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054806

RESUMO

Plants have been extensively studied since ancient times and numerous important chemical constituents with tremendous therapeutic potential are identified. Attacks of microorganisms including viruses and bacteria can be counteracted with an efficient immune system and therefore, stimulation of body's defense mechanism against infections has been proven to be an effective approach. Polysaccharides, terpenoids, flavonoids, alkaloids, glycosides, and lactones are the important phytochemicals, reported to be primarily responsible for immunomodulation activity of the plants. These phytochemicals may act as lead molecules for the development of safe and effective immunomodulators as potential remedies for the prevention and cure of viral diseases. Natural products are known to primarily modulate the immune system in nonspecific ways. A number of plant-based principles have been identified and isolated with potential immunomodulation activity which justify their use in traditional folklore medicine and can form the basis of further specified research. The aim of the current review is to describe and highlight the immunomodulation potential of certain plants along with their bioactive chemical constituents. Relevant literatures of recent years were searched from commonly employed scientific databases on the basis of their ethnopharmacological use. Most of the plants displaying considerable immunomodulation activity are summarized along with their possible mechanisms. These discussions shall hopefully elicit the attention of researchers and encourage further studies on these plant-based immunomodulation products as potential therapy for the management of infectious diseases, including viral ones such as COVID-19.


Assuntos
Produtos Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , Terapias Complementares/métodos , Fitoterapia/métodos , Preparações de Plantas/uso terapêutico , SARS-CoV-2/fisiologia , Viroses/tratamento farmacológico , Animais , Humanos , Imunomodulação , Plantas Medicinais , Terpenos/uso terapêutico
8.
Vet J ; 271: 105648, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33840487

RESUMO

Interferons (IFNs) are cytokines that play an important role in the immune response of animals and humans. A number of studies reviewed here have evaluated the use of human, canine and feline IFNs as treatments for infectious, inflammatory and neoplastic disease in dogs and cats. Recombinant canine IFN-γ is deemed an efficacious therapy for canine atopic dermatitis. Recombinant feline IFN-ω is effective against canine parvoviral enteritis and has also been recommended for canine atopic dermatitis. Based on limited evidence, recombinant canine IFN-α could be a topical treatment option for dogs with gingivitis and keratoconjunctivitis sicca. Conclusive evidence is lacking for other diseases and large randomised controlled trials are needed before IFNs can be recommended for other indications.


Assuntos
Doenças do Gato/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Interferons/uso terapêutico , Animais , Gatos , Cães , Gengivite/tratamento farmacológico , Humanos , Infecções/tratamento farmacológico , Infecções/veterinária , Inflamação/tratamento farmacológico , Inflamação/veterinária , Interferon-alfa/uso terapêutico , Ceratoconjuntivite Seca/tratamento farmacológico , Ceratoconjuntivite Seca/veterinária , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Proteínas Recombinantes/uso terapêutico , Viroses/tratamento farmacológico , Viroses/veterinária
9.
Adv Sci (Weinh) ; 8(7): 2003895, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33850691

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has quickly and deeply affected the world, with over 60 million confirmed cases. There has been a great effort worldwide to contain the virus and to search for an effective treatment for patients who become critically ill with COVID-19. A promising therapeutic compound currently undergoing clinical trials for COVID-19 is nitric oxide (NO), which is a free radical that has been previously reported to inhibit the replication of several DNA and RNA viruses, including coronaviruses. Although NO has potent antiviral activity, it has a complex role in the immunological host responses to viral infections, i.e., it can be essential for pathogen control or detrimental for the host, depending on its concentration and the type of virus. In this Essay, the antiviral role of NO against SARS-CoV, SARS-CoV-2, and other human viruses is highlighted, current development of NO-based therapies used in the clinic is summarized, existing challenges are discussed and possible further developments of NO to fight viral infections are suggested.


Assuntos
Antivirais/uso terapêutico , Óxido Nítrico/uso terapêutico , Viroses/tratamento farmacológico , Antivirais/química , Antivirais/farmacologia , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/virologia , Ensaios Clínicos como Assunto , Humanos , Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Viroses/patologia , Replicação Viral/efeitos dos fármacos
10.
Immunol Res ; 69(2): 117-128, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33834387

RESUMO

The continuous emergence of infectious pathogens along with antimicrobial resistance creates a need for an alternative approach to treat infectious diseases. Targeting host factor(s) which are critically involved in immune signaling pathways for modulation of host immunity offers to treat a broad range of infectious diseases. Upon pathogen-associated ligands binding to the Toll-like/ IL-1R family, and other cellular receptors, followed by recruitment of intracellular signaling adaptor proteins, primarily MyD88, trigger the innate immune responses. But activation of host innate immunity strongly depends on the correct function of MyD88 which is tightly regulated. Dysregulation of MyD88 may cause an imbalance that culminates to a wide range of inflammation-associated syndromes and diseases. Furthermore, recent reports also describe that MyD88 upregulation with many viral infections is linked to decreased antiviral type I IFN response, and MyD88-deficient mice showed an increase in survivability. These reports suggest that MyD88 is also negatively involved via MyD88-independent pathways of immune signaling for antiviral type I IFN response. Because of its expanding role in controlling host immune signaling pathways, MyD88 has been recognized as a potential drug target in a broader drug discovery paradigm. Targeting BB-loop of MyD88, small molecule inhibitors were designed by structure-based approach which by blocking TIR-TIR domain homo-dimerization have shown promising therapeutic efficacy in attenuating MyD88-mediated inflammatory impact, and increased antiviral type I IFN response in experimental mouse model of diseases. In this review, we highlight the reports on MyD88-linked immune response and MyD88-targeted therapeutic approach with underlying mechanisms for controlling inflammation and antiviral type I IFN response. HIGHLIGHTS: • Host innate immunity is activated upon PAMPs binding to PRRs followed by immune signaling through TIR domain-containing adaptor proteins mainly MyD88. • Structure-based approach led to develop small-molecule inhibitors which block TIR domain homodimerization of MyD88 and showed therapeutic efficacy in limiting severe inflammation-associated impact in mice. • Therapeutic intervention of MyD88 also showed an increase in antiviral effect with strong type I IFN signaling linked to increased phosphorylation of IRFs via MyD88-independent pathway. • MyD88 inhibitors might be potentially useful as a small-molecule therapeutics for modulation of host immunity against inflammatory diseases and antiviral therapy. • However, prior clinical use of more in-depth efforts should be focused for suitability of the approach in deploying to complex diseases including COPD and COVID-19 in limiting inflammation-associated syndrome to infection.


Assuntos
Sistemas de Liberação de Medicamentos , Imunidade Inata/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide , Viroses , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , Fator 88 de Diferenciação Mieloide/imunologia , Viroses/tratamento farmacológico , Viroses/imunologia
11.
Int J Mol Sci ; 22(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920628

RESUMO

Viral infections cause a host of fatal diseases and seriously affect every form of life from bacteria to humans. Although most viral infections can receive appropriate treatment thereby limiting damage to life and livelihood with modern medicine and early diagnosis, new types of viral infections are continuously emerging that need to be properly and timely treated. As time is the most important factor in the progress of many deadly viral diseases, early detection becomes of paramount importance for effective treatment. Aptamers are small oligonucleotide molecules made by the systematic evolution of ligands by exponential enrichment (SELEX). Aptamers are characterized by being able to specifically bind to a target, much like antibodies. However, unlike antibodies, aptamers are easily synthesized, modified, and are able to target a wider range of substances, including proteins and carbohydrates. With these advantages in mind, many studies on aptamer-based viral diagnosis and treatments are currently in progress. The use of aptamers for viral diagnosis requires a system that recognizes the binding of viral molecules to aptamers in samples of blood, serum, plasma, or in virus-infected cells. From a therapeutic perspective, aptamers target viral particles or host cell receptors to prevent the interaction between the virus and host cells or target intracellular viral proteins to interrupt the life cycle of the virus within infected cells. In this paper, we review recent attempts to use aptamers for the diagnosis and treatment of various viral infections.


Assuntos
Antivirais/uso terapêutico , Aptâmeros de Nucleotídeos/uso terapêutico , Viroses/diagnóstico , Viroses/tratamento farmacológico , Animais , Vírus de DNA/efeitos dos fármacos , Humanos , Vírus de RNA/efeitos dos fármacos , Proteínas Virais/efeitos dos fármacos , Vírion/efeitos dos fármacos
12.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808471

RESUMO

Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication and contribute to the pathogenesis of virus-induced disease. Redox homeostasis has an important role in maintaining an appropriate Th1/Th2 balance, which is necessary to mount an effective immune response against viral infection and to avoid excessive inflammatory responses. It is known that excessive production of reactive oxygen species (ROS) induced by viral infection activates nuclear factor (NF)-kB, which orchestrates the expression of viral and host genes involved in the viral replication and inflammatory response. Moreover, redox-regulated protein disulfide isomerase (PDI) chaperones have an essential role in catalyzing formation of disulfide bonds in viral proteins. This review aims at describing the role of GSH in modulating redox sensitive pathways, in particular that mediated by NF-kB, and PDI activity. The second part of the review discusses the effectiveness of GSH-boosting molecules as broad-spectrum antivirals acting in a multifaceted way that includes the modulation of immune and inflammatory responses.


Assuntos
Glutationa/metabolismo , Viroses/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/farmacologia , Humanos , NF-kappa B/metabolismo , Oxirredução/efeitos dos fármacos , Isomerases de Dissulfetos de Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Viroses/metabolismo
13.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804765

RESUMO

The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research.


Assuntos
Leptina/imunologia , Leptina/metabolismo , Obesidade/complicações , Obesidade/virologia , Viroses/complicações , Animais , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/metabolismo , Metabolismo Energético/imunologia , Humanos , Sistema Imunitário/metabolismo , Sistema Imunitário/virologia , Obesidade/imunologia , Obesidade/metabolismo , Vacinas Virais/uso terapêutico , Viroses/tratamento farmacológico , Viroses/imunologia , Viroses/metabolismo
14.
ACS Appl Mater Interfaces ; 13(18): 20995-21006, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33930273

RESUMO

COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Inflamação/tratamento farmacológico , Nanopartículas/uso terapêutico , Viroses/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Antioxidantes/uso terapêutico , Antivirais/química , COVID-19/tratamento farmacológico , Proteínas do Nucleocapsídeo de Coronavírus/farmacologia , Citocinas/metabolismo , Feminino , Ácido Glicirrízico/química , Humanos , Fígado/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Hepatite Murina/efeitos dos fármacos , Nanopartículas/química , Fosfoproteínas/farmacologia , Células RAW 264.7 , SARS-CoV-2/química , Células THP-1 , Carga Viral/efeitos dos fármacos , Viroses/patologia , Replicação Viral/efeitos dos fármacos
15.
Arch Immunol Ther Exp (Warsz) ; 69(1): 10, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33811524

RESUMO

The review discusses a new approach to the prevention and treatment of viral infections based on the use of pine needles polyprenyl phosphate (PPP) and associated with the infringement of prenylation process-the attachment of farnesol or geranyl geraniol to the viral protein. Currently, prenylation has been detected in type 1 adenovirus, hepatitis C virus, several herpes viruses, influenza virus, HIV. However, this list is far from complete, given that prenylated proteins play an extremely important role in the activity of the virus. We assume that the interferon produced in response to PPP may suppress expression of the SREBP2 transcription factor. As a result, the mevalonic acid pathway is violated and, as a result, the formation of early polyprenols precursors (geraniol, geranyl geraniol, farnesol), which are necessary for the prenylation of viral proteins, is blocked and the formation of mature, virulent virus particles is broken. As a consequence, the maturation of viral particles is inhibited, and defective particles are formed. Polyprenol was extracted from greenery (pine, fir and spruce needles, mulberry leaves, etc.), purified by chromatography, phosphorylated and identified by HPLC and NMR. Obtained PPP was used as antiviral in some experimental models in vitro and in vivo. During numerous studies, it was found that PPP manifested versatile antiviral effects, both in vitro and in vivo. The maximum effect was observed with viruses in which the presence of prenylated proteins was established, namely influenza A virus, HIV-1, tick-borne encephalitis virus, hepatitis A and C viruses, herpes simplex viruses type 1 and 2, some coronavirus. The available data obtained both in the experimental conditions and during clinical trials allow us to regard PPPs as safe and effective medicine for prevention and treatment of viral diseases.


Assuntos
Antivirais/farmacologia , Pinus/química , Fosfatos de Poli-Isoprenil/farmacologia , Prenilação de Proteína/efeitos dos fármacos , Viroses/tratamento farmacológico , Animais , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Interferons/metabolismo , Microscopia Eletrônica , Fosfatos de Poli-Isoprenil/uso terapêutico , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Resultado do Tratamento , Proteínas Virais/metabolismo , Vírion/efeitos dos fármacos , Vírion/ultraestrutura , Viroses/imunologia , Viroses/prevenção & controle , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
16.
Biomolecules ; 11(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920915

RESUMO

Matrix metalloproteinases (MMPs) cleave extracellular matrix proteins, growth factors, cytokines, and receptors to influence organ development, architecture, function, and the systemic and cell-specific responses to diseases and pharmacological drugs. Conversely, many diseases (such as atherosclerosis, arthritis, bacterial infections (tuberculosis), viral infections (COVID-19), and cancer), cholesterol-lowering drugs (such as statins), and tetracycline-class antibiotics (such as doxycycline) alter MMP activity through transcriptional, translational, and post-translational mechanisms. In this review, we summarize evidence that the aforementioned diseases and drugs exert significant epigenetic pressure on genes encoding MMPs, tissue inhibitors of MMPs, and factors that transcriptionally regulate the expression of MMPs. Our understanding of human pathologies associated with alterations in the proteolytic activity of MMPs must consider that these pathologies and their medicinal treatments may impose epigenetic pressure on the expression of MMP genes. Whether the epigenetic mechanisms affecting the activity of MMPs can be therapeutically targeted warrants further research.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas , Epigênese Genética/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Metaloproteinases da Matriz/genética , Tetraciclinas/farmacologia , Animais , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/genética , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/genética , COVID-19/tratamento farmacológico , COVID-19/genética , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/genética , Tetraciclinas/uso terapêutico , Viroses/tratamento farmacológico , Viroses/genética
17.
Gene ; 783: 145574, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33737124

RESUMO

Epidemiological and clinical evidence suggests that Bacille Calmette-Guérin (BCG) vaccine induced trained immunity protects against non-specific infections. Multiple clinical trials are currently underway to assess effectiveness of the vaccine in the coronavirus disease 2019 (COVID-19). However, the durability and mechanism of BCG trained immunity remain unclear. Here, an integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and respiratory tract viral infections as well as of reported transcriptomic alterations in COVID-19 is presented toward addressing this gap. Results suggest that the vaccine induces very long-lasting transcriptomic changes that mimic viral infections by, consistent with the present concept of trained immunity, upregulation of antiviral defense response, and oppose viral infections by, inconsistent with the concept, downregulation of myeloid cell activation. These durability and mechanistic insights argue against possible indiscriminate use of the vaccine and activated innate immune response associated safety concerns in COVID-19, in that order.


Assuntos
Antivirais/uso terapêutico , Vacina BCG/uso terapêutico , COVID-19/tratamento farmacológico , Viroses/tratamento farmacológico , Adulto , Vacina BCG/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , Criança , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Lactente , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Transcriptoma , Viroses/imunologia
18.
Medicina (Kaunas) ; 57(2)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33673004

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic and is posing a serious challenge to mankind. As per the current scenario, there is an urgent need for antiviral that could act as a protective and therapeutic against SARS-CoV-2. Previous studies have shown that SARS-CoV-2 is much similar to the SARS-CoV bat that occurred in 2002-03. Since it is a zoonotic virus, the exact source is still unknown, but it is believed bats may be the primary reservoir of SARS-CoV-2 through which it has been transferred to humans. In this review, we have tried to summarize some of the approaches that could be effective against SARS-CoV-2. Firstly, plants or plant-based products have been effective against different viral diseases, and secondly, plants or plant-based natural products have the minimum adverse effect. We have also highlighted a few vitamins and minerals that could be beneficial against SARS-CoV-2.


Assuntos
Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , Nutrientes/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Viroses/tratamento farmacológico , Animais , Quirópteros/virologia , Humanos
19.
Cell ; 184(6): 1604-1620, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33740455

RESUMO

Historically, emerging viruses appear constantly and have cost millions of human lives. Currently, climate change and intense globalization have created favorable conditions for viral transmission. Therefore, effective antivirals, especially those targeting the conserved protein in multiple unrelated viruses, such as the compounds targeting RNA-dependent RNA polymerase, are urgently needed to combat more emerging and re-emerging viruses in the future. Here we reviewed the development of antivirals with common targets, including those against the same protein across viruses, or the same viral function, to provide clues for development of antivirals for future epidemics.


Assuntos
Antivirais/uso terapêutico , Doenças Transmissíveis Emergentes/tratamento farmacológico , Doenças Transmissíveis Emergentes/epidemiologia , Terapia de Alvo Molecular/métodos , Pandemias , Viroses/tratamento farmacológico , Viroses/epidemiologia , Vírus/enzimologia , Animais , Antivirais/farmacologia , Doenças Transmissíveis Emergentes/virologia , Humanos , RNA Polimerase Dependente de RNA/antagonistas & inibidores , Proteínas do Envelope Viral/antagonistas & inibidores , Viroses/virologia , Internalização do Vírus/efeitos dos fármacos
20.
Cells ; 10(2)2021 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-33669990

RESUMO

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.


Assuntos
Redes e Vias Metabólicas , Sirtuínas/metabolismo , Viroses/metabolismo , Animais , Antivirais/química , Antivirais/farmacologia , Descoberta de Drogas , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Modelos Moleculares , Terapia de Alvo Molecular , NAD/metabolismo , Sirtuínas/análise , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Vírus/metabolismo
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