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1.
J Pharm Pharmacol ; 73(3): 281-299, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33793885

RESUMO

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.


Assuntos
Antivirais/imunologia , Antivirais/uso terapêutico , /imunologia , Fatores Imunológicos/uso terapêutico , Própole/imunologia , Própole/uso terapêutico , Animais , Humanos , Fatores Imunológicos/imunologia , /imunologia
2.
Int J Mol Sci ; 22(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673372

RESUMO

One of the most severe effects of coronavirus disease 2019 (COVID-19) is lung disorders such as acute respiratory distress syndrome. In the absence of effective treatments, it is necessary to search for new therapies and therapeutic targets. Platelets play a fundamental role in respiratory disorders resulting from viral infections, being the first line of defense against viruses and essential in maintaining lung function. The direct application of platelet lysate (PL) obtained from the platelet-rich plasma of healthy donors could help in the improvement of the patient due its anti-inflammatory, immunomodulatory, antifibrotic, and repairing effects. This work evaluates PL nebulization by analyzing its levels of growth factors and its biological activity on lung fibroblast cell cultures, besides describing a scientific basis for its use in this kind of pathology. The data of the work suggest that the molecular levels and biological activity of the PL are maintained after nebulization. Airway administration would allow acting directly on the lung tissue modulating inflammation and stimulating reparative processes on key structures such as the alveolocapillary barrier, improving the disease and sequels. The protocol developed in this work is a first step for the study of nebulized PL both in animal experimentation and in clinical trials.


Assuntos
Anti-Inflamatórios/farmacologia , Fatores Imunológicos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Plasma Rico em Plaquetas , Adulto , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/imunologia , Plaquetas/imunologia , Linhagem Celular , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Masculino , Nebulizadores e Vaporizadores , Plasma Rico em Plaquetas/imunologia , Resultado do Tratamento
3.
Washington; PAHO; Jan. 29, 2021. 195 p.
Não convencional em Inglês | PIE | ID: biblio-1146643

RESUMO

The vast amount of data generated by clinical studies of potential therapeutic options for COVID-19 presents important challenges. This new information must be interpreted quickly so that prescribers can make optimal treatment decisions with as little harm to patients as possible, and so that medicines manufacturers can scale-up production rapidly and bolster their supply chains. Interpreting new data quickly will save lives by ensuring that reportedly successful drugs can be administered to as many patients as possible as quickly as possible. The fifteenth edition of this database of evidence on potential therapeutic options for COVID-19 examines 79 therapeutic options. This information will help investigators, policy makers, and prescribers navigate the flood of relevant data to ensure that management of COVID-19, at both individual and population levels, is based on the best available knowledge. This resource will be continually updated as more research is released into the public space.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pandemias/prevenção & controle , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Fatores Imunológicos/imunologia
4.
Int J Mol Sci ; 22(3)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498909

RESUMO

The prevention and control of infectious diseases is crucial to the maintenance and protection of social and public healthcare. The global impact of SARS-CoV-2 has demonstrated how outbreaks of emerging and re-emerging infections can lead to pandemics of significant public health and socio-economic burden. Vaccination is one of the most effective approaches to protect against infectious diseases, and to date, multiple vaccines have been successfully used to protect against and eradicate both viral and bacterial pathogens. The main criterion of vaccine efficacy is the induction of specific humoral and cellular immune responses, and it is well established that immunogenicity depends on the type of vaccine as well as the route of delivery. In addition, antigen delivery to immune organs and the site of injection can potentiate efficacy of the vaccine. In light of this, microvesicles have been suggested as potential vehicles for antigen delivery as they can carry various immunogenic molecules including proteins, nucleic acids and polysaccharides directly to target cells. In this review, we focus on the mechanisms of microvesicle biogenesis and the role of microvesicles in infectious diseases. Further, we discuss the application of microvesicles as a novel and effective vaccine delivery system.


Assuntos
/prevenção & controle , Vesículas Extracelulares/imunologia , Fatores Imunológicos/imunologia , Vacinas Virais/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Vacinação/métodos , Vacinas Virais/imunologia
5.
Methods Mol Biol ; 2225: 107-123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108660

RESUMO

Viruses have devised highly effective approaches that modulate the host immune response, blocking immune responses that are designed to eradicate viral infections. Over millions of years of evolution, virus-derived immune-modulating proteins have become extraordinarily potent, in some cases working at picomolar concentrations when expressed into surrounding tissues and effectively blocking host defenses against viral invasion and replication. The marked efficiency of these immune-modulating proteins is postulated to be due to viral engineering of host immune modulators as well as design and development of new strategies (i.e., some derived from host proteins and some entirely unique). Two key characteristics of viral immune modulators confer both adaptive advantages and desirable functions for therapeutic translation. First, many virus-derived immune modulators have evolved structures that are not readily recognized or regulated by mammalian immune pathways, ensuring little to no neutralizing antibody responses or proteasome-mediated degradation. Second, these immune modulators tend to target early steps in central immune responses, producing a powerful downstream inhibitory "domino effect" which may alter cell activation and gene expression.We have proposed that peptide metabolites of these immune-modulating proteins can enhance and extend protein function. Active immunomodulating peptides have been derived from both mammalian and viral proteins. We previously demonstrated that peptides derived from computationally predicted cleavage sites in the reactive center loop (RCL) of a viral serine proteinase inhibitor (serpin ) from myxoma virus, Serp-1 , can modify immune response activation. We have also demonstrated modulation of host gut microbiota produced by Serp-1 and RCL-derived peptide , S7, in a vascular inflammation model. Of interest, generation of derived peptides that maintain therapeutic function from a serpin can act by a different mechanism. Whereas Serp-1 has canonical serpin-like function to inhibit serine proteases, S7 instead targets mammalian serpins. Here we describe the derivation of active Serp- RCL peptides and their testing in inflammatory vasculitis models.


Assuntos
Fatores Imunológicos/imunologia , Myxoma virus/genética , Peptídeos/imunologia , Serpinas/imunologia , Transplante Homólogo/métodos , Vasculite/terapia , Proteínas Virais/imunologia , Animais , Aorta Torácica , Modelos Animais de Doenças , Feminino , Expressão Gênica , Fatores Imunológicos/genética , Fatores Imunológicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptídeos/genética , Peptídeos/farmacologia , Receptores de Interferon/deficiência , Receptores de Interferon/genética , Serpinas/genética , Serpinas/farmacologia , Vasculite/imunologia , Vasculite/patologia , Proteínas Virais/genética , Proteínas Virais/farmacologia
6.
Methods Mol Biol ; 2225: 217-226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108665

RESUMO

Immune modulators play critical roles in the progression of wounds to normal or conversely delayed healing, through the regulation of normal tissue regrowth, scarring, inflammation, and growth factor expression. Many immune modulator recombinants are under active preclinical study or in clinical trial to promote improved acute or chronic wound healing and to reduce scarring. Viruses have evolved highly efficient immune modulators for the evasion of host-defensive immune responses that target and kill invasive viruses. Recent studies have proven that some of these virus-derived immune modulators can be used to promote wound healing with significantly improved speed and reduced scarring in rodent models. Mouse full-thickness excisional wound model is one of the most commonly used animal models used to study wound healing for its similarity to humans in the healing phases and associated cellular and molecular mechanisms. This chapter introduces this mouse dermal wound healing model in detail for application in studying viral immune modulators as new treatments to promote wound healing. Details of hydrogel, protein construction, and topical application methods for these therapeutic proteins are provided in this chapter.


Assuntos
Cicatriz/prevenção & controle , Fatores Imunológicos/farmacologia , Myxoma virus/química , Ferida Cirúrgica/tratamento farmacológico , Proteínas Virais/farmacologia , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Quitosana/química , Cicatriz/genética , Cicatriz/imunologia , Cicatriz/patologia , Colágeno Tipo I/biossíntese , Colágeno Tipo I/genética , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Feminino , Expressão Gênica , Hidrogéis/química , Fatores Imunológicos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pele/efeitos dos fármacos , Pele/lesões , Ferida Cirúrgica/genética , Ferida Cirúrgica/imunologia , Ferida Cirúrgica/patologia , Proteínas Virais/imunologia , Cicatrização/imunologia
7.
Methods Mol Biol ; 2225: 227-239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108666

RESUMO

Severe inflammatory disease initiated by neurotrauma and stroke is of primary concern in these intractable pathologies as noted in recent studies and understanding of the pathogenesis of spinal cord injury (SCI) in the rat model. Successful anti-inflammatory treatments should result in neuroprotection and limit the loss of neurological function to injury caused by the initial damage. Continuous subdural infusion offers direct access to the cavity of injury (COI) that forms after balloon crush SCI deep in the spinal cord. Some anti-inflammatory compounds are not likely capable of crossing the blood-spinal cord barrier. Subdural infusion of myxoma virus-derived Serp-1, an anti-thrombotic/anti-thrombolytic, and also of M-T7, a chemokine inhibitor, improved the locomotor scores and pain sensation scores as well as reduced the numbers of macrophages in the COI by 50 and 80%, respectively, while intraperitoneal infusion of either protein had little effect. Injection of a chitosan hydrogel loaded with Serp-1 into the dorsal spinal column crush also resulted in improved neurological deficits and in reduction of the size of the crush lesion 4 weeks after injury. While neurological scores in a simplified hind-end (HE) locomotor test together with a toe-pinch withdrawal test demonstrated improvement in all balloon crush injury and dorsal spinal crush injury rats, a severe inflammation is induced by the injury indicating additional damage to the spinal cord. Thus neurological function testing can be contradictory, rather than corresponding, to the pathogenesis of SCI. The count of macrophages in the COI offers a precise, reliable method of measuring the effectiveness of a neuroprotective treatment of SCI in preclinical studies.


Assuntos
Anti-Inflamatórios/farmacologia , Fatores Imunológicos/farmacologia , Myxoma virus/química , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Proteínas Virais/farmacologia , Animais , Anti-Inflamatórios/imunologia , Quitosana/química , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Fatores Imunológicos/imunologia , Injeções Epidurais , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/imunologia , Ratos , Ratos Long-Evans , Receptores de Interferon/imunologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologia , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/patologia , Proteínas Virais/imunologia
8.
Methods Mol Biol ; 2225: 241-255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108667

RESUMO

Systemic lupus erythematosus (SLE) is a multifactorial and heterogeneous autoimmune disease involving multiple organ systems and tissues. Lupus nephritis occurs in approximately 60% of patients with SLE and is the leading cause of morbidity. Diffuse alveolar hemorrhage (DAH) is a rare but very serious complication of SLE with a greater than 50% associated mortality. The etiology of SLE is unclear but has proposed genetic, hormonal, and environmental aspects. Pristane is a saturated terpenoid alkane and has become the most popular laboratory model for inducing lupus in mice. The pristane model of SLE has the capacity to reproduce many components of the human presentation of the disease. Previous studies have demonstrated that virus-derived immune-modulating proteins have the potential to control inflammatory and autoimmune disorders. Serp-1, a 55 kDa secreted and highly glycosylated immune modulator derived from myxoma virus (MYXV), has potent immunomodulatory activity in models of vasculitis, viral sepsis, collagen-induced arthritis, and transplant rejection. This chapter describes the mouse preclinical pristane lupus model as a method to examine virus-derived protein efficacy for treating autoimmune diseases and specifically lupus nephritis and DAH.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Hemorragia/prevenção & controle , Fatores Imunológicos/farmacologia , Nefrite Lúpica/tratamento farmacológico , Myxoma virus/química , Proteinúria/tratamento farmacológico , Proteínas Virais/farmacologia , Animais , Autoanticorpos/biossíntese , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Hemorragia/imunologia , Hemorragia/patologia , Humanos , Fatores Imunológicos/imunologia , Injeções Intraperitoneais , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteinúria/induzido quimicamente , Proteinúria/imunologia , Proteinúria/patologia , Terpenos/administração & dosagem , Resultado do Tratamento , Proteínas Virais/imunologia
9.
Methods Mol Biol ; 2225: 257-273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108668

RESUMO

Solid tissue transplant is a growing medical need that is further complicated by a limited donor organ supply. Acute and chronic rejection occurs in nearly all transplants and reduces long-term graft survival, thus increasing the need for repeat transplantation. Viruses have evolved highly adapted responses designed to evade the host's immune defenses. Immunomodulatory proteins derived from viruses represent a novel class of potential therapeutics that are under investigation as biologics to attenuate immune-mediated rejection and damage. These immune-modulating proteins have the potential to reduce the need for traditional posttransplant immune suppressants and improve graft survival. The myxoma virus-derived protein M-T7 is a promising biologic that targets chemokine and glycosaminoglycan pathways central to kidney transplant rejection. Orthotopic transplantations in mice are prohibitively difficult and costly and require a highly trained microsurgeon to successfully perform the procedure. Here we describe a kidney-to-kidney subcapsular transplant model as a practical and simple method for studying transplant rejection, a model that requires fewer mice. One kidney can be used as a donor for transplants into six or more recipient mice. Using this model there is lower morbidity, pain, and mortality for the mice. Subcapsular kidney transplantation provides a first step approach to testing virus-derived proteins as new potential immune-modulating therapeutics to reduce transplant rejection and inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Fatores Imunológicos/farmacologia , Transplante de Rim/métodos , Myxoma virus/química , Proteínas Virais/farmacologia , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/metabolismo , Biomarcadores/análise , Quimiocinas/biossíntese , Complemento C4b/genética , Complemento C4b/imunologia , Feminino , Expressão Gênica , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Fatores Imunológicos/biossíntese , Fatores Imunológicos/imunologia , Rim/imunologia , Rim/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Receptores de Interferon/biossíntese , Receptores de Interferon/imunologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Transplante Homólogo , Proteínas Virais/biossíntese , Proteínas Virais/imunologia
10.
Methods Mol Biol ; 2225: 275-292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108669

RESUMO

Ischemia-reperfusion injury (IRI) drives early and long-term damage to organs as well as compounding damage from acute transplant rejection and surgical trauma. IRI initiates an aggressive and prolonged inflammation leading to tissue injury, organ failure, and death. However, there are few effective therapeutic interventions for IRI. The destructive inflammatory cell activity in IRI is part of an aberrant innate immune response that triggers multiple pathways. Hence, immune-modulating treatments to control pathways triggered by IRI hold great therapeutic potential. Viruses, especially large DNA viruses, have evolved highly effective immune-modulating proteins for the purpose of immune evasion and to protect the virus from the host immune defenses. A number of these immune-modulating proteins have proven therapeutically effective in preclinical models, many with function targeting pathways known to be involved in IRI. The use of virus-derived immune-modulating proteins thus represents a promising source for new treatments to target ischemia-reperfusion injury. Laboratory small animal models of IRI are well established and are able to reproduce many aspects of ischemia-reperfusion injury seen in humans. This chapter will discuss the methods used to perform the IRI procedure in mice, as well as clinically relevant diagnostic tests to evaluate liver injury and approaches for assessing histological damage while testing novel immune modulating protein treatments.


Assuntos
Anti-Inflamatórios/farmacologia , Hepatite/prevenção & controle , Fatores Imunológicos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Proteínas Virais/farmacologia , Isquemia Quente/métodos , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/metabolismo , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Hepatite/genética , Hepatite/imunologia , Hepatite/patologia , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/biossíntese , Fatores Imunológicos/imunologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/imunologia , Fígado/patologia , Camundongos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Coloração e Rotulagem/métodos , Proteínas Virais/biossíntese , Proteínas Virais/imunologia
11.
Scand J Immunol ; 93(2): e13017, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33351196

RESUMO

The neonatal Fc receptor (FcRn) was first recognized for its role in transfer of maternal IgG to the foetus or newborn, providing passive immunity early in life. However, it has become clear that the receptor is versatile, widely expressed and plays an indispensable role in both immunological and non-immunological processes throughout life. The receptor rescues immunoglobulin G (IgG) and albumin from intracellular degradation and shuttles the ligands across polarized cell barriers, in all cases via a pH-dependent binding-and-release mechanism. These processes secure distribution and high levels of both IgG and albumin throughout the body. At mucosal sites, FcRn transports IgG across polarized epithelial cells where it retrieves IgG in complex with luminal antigens that is delivered to tissue-localized immune cells. In dendritic cells (DCs), FcRn orchestrates processing of IgG-opsonized immune complexes (ICs) in concert with classical Fcγ receptors, which results in antigen presentation and cross-presentation of antigenic peptides on MHC class II and I to CD4+ and CD8+ T cells, respectively. Hence, FcRn regulates transport of the ligands within and across different types of cells, but also processing of IgG-ICs by immune cells. As such, the receptor is involved in immune surveillance and protection against infections. In this brief review, we highlight how FcRn expressed by hematopoietic and non-hematopoietic cells contributes to immune regulation at mucosal barriers-biology that can be utilized in development of biologics and subunit vaccines for non-invasive delivery.


Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Membrana Mucosa/imunologia , Receptores Fc/imunologia , Animais , Apresentação do Antígeno/imunologia , Complexo Antígeno-Anticorpo/imunologia , Antígenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Humanos , Imunoglobulina G/imunologia , Fatores Imunológicos/imunologia
12.
Washington; PAHO; Dec. 18, 2020. 163 p.
Não convencional em Inglês | LILACS, PIE | ID: biblio-1145577

RESUMO

This is the thirteenth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, pregnant women, those with immune conditions, etc.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pandemias/prevenção & controle , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Fatores Imunológicos/imunologia
13.
Washington; PAHO; Nov. 13, 2020. 128 p.
Não convencional em Inglês | LILACS, PIE | ID: biblio-1140054

RESUMO

This is the twelfth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pandemias/prevenção & controle , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Fatores Imunológicos/imunologia
14.
Washington; PAHO; Nov. 30, 2020. 131 p.
Não convencional em Inglês | LILACS, PIE | ID: biblio-1140053

RESUMO

This is the twelfth edition of this summary of rapid systematic reviews, which includes the results of currently available literature. More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review, 58 therapeutic options are examined. The Pan American Health Organization (PAHO) is continually monitoring ongoing research on any possible therapeutic options. As evidence emerges, then PAHO will immediately assess and update its position, and particularly as it applies to any special sub-group populations such as children, expectant mothers, those with immune conditions, etc.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Pandemias/prevenção & controle , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Fatores Imunológicos/imunologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-33031994

RESUMO

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.


Assuntos
Ansiedade/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Depressão/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Ansiedade/imunologia , Ansiedade/metabolismo , Ansiedade/virologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Citocinas/biossíntese , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/virologia , Depressão/imunologia , Depressão/metabolismo , Depressão/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/virologia , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/imunologia , Fatores Imunológicos/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/virologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia
16.
Front Immunol ; 11: 558898, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072097

RESUMO

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This "cytokine storm" produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities. In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1, and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases and conditions often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Pneumonia Viral/imunologia , /imunologia , Infecções por Coronavirus/mortalidade , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/mortalidade , Pandemias , Pneumonia Viral/mortalidade , /patologia , /virologia
17.
Viruses ; 12(9)2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967229

RESUMO

As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.


Assuntos
Fatores Imunológicos/imunologia , Viroses/imunologia , Vírus/imunologia , Animais , Antivirais/uso terapêutico , Doença Crônica , Humanos , Fatores Imunológicos/antagonistas & inibidores , Imunoterapia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Viroses/terapia , Vírus/classificação
18.
Int J Nanomedicine ; 15: 5181-5202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801685

RESUMO

Background: Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses. Materials and Methods: In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model. Results: Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1ß) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model. Conclusion: Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antivirais/farmacologia , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Nanopartículas/química , Pró-Fármacos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/imunologia , Antivirais/imunologia , Citocinas/metabolismo , Cães , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Edema/tratamento farmacológico , Edema/metabolismo , Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Quercetina/imunologia , Quercetina/farmacologia , Ratos , Ácido Chiquímico/imunologia , Ácido Chiquímico/farmacologia , Dióxido de Silício/química
20.
Aging Clin Exp Res ; 32(9): 1879-1881, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705585

RESUMO

In the search for factors affecting incidence and lethality of the current COVID-19 pandemic, recent association studies explored the possible role of vitamin D deficiency. Altogether, these studies, in most cases based on cross-sectional analyses, could not yet provide a convincing demonstration of a cause-effect relationship. In this editorial, the authors describe the scientific evidence underlying a possible role of vitamin D in the prevention and development of the pandemic, considering its immunomodulatory role and antiviral effects. They conclude that further studies are needed to (1) better explore possible associations between vitamin D deficiency and COVID-19 morbidity and lethality, and (2) assess if compensating such deficiency could avoid or mitigate the worst manifestations of COVID-19. They highlight the need for public health campaigns to promote consumption of vitamin D-rich foods and proper sunlight exposition or, when this is not possible, controlled pharmaceutical supplementation, especially in countries with high prevalence of hypovitaminosis D.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Deficiência de Vitamina D , Vitamina D , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/prevenção & controle , Suplementos Nutricionais , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/prevenção & controle , Prevalência , Vitamina D/imunologia , Vitamina D/farmacologia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/terapia
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