Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.527
Filtrar
1.
Int J Mol Sci ; 21(14)2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32674481

RESUMO

Effective treatment of retinal diseases with adeno-associated virus (AAV)-mediated gene therapy is highly dependent on the proportion of successfully transduced cells. However, due to inflammatory reactions at high vector doses, adjunctive treatment may be necessary to enhance the therapeutic outcome. Hydroxychloroquine and chloroquine are anti-malarial drugs that have been successfully used in the treatment of autoimmune diseases. Evidence suggests that at high concentrations, hydroxychloroquine and chloroquine can impact viral infection and replication by increasing endosomal and lysosomal pH. This effect has led to investigations into the potential benefits of these drugs in the treatment of viral infections, including human immunodeficiency virus and severe acute respiratory syndrome coronavirus-2. However, at lower concentrations, hydroxychloroquine and chloroquine appear to exert immunomodulatory effects by inhibiting nucleic acid sensors, including toll-like receptor 9 and cyclic GMP-AMP synthase. This dose-dependent effect on their mechanism of action supports observations of increased viral infections associated with lower drug doses. In this review, we explore the immunomodulatory activity of hydroxychloroquine and chloroquine, their impact on viral infections, and their potential to improve the efficacy and safety of retinal gene therapy by reducing AAV-induced immune responses. The safety and practicalities of delivering hydroxychloroquine into the retina will also be discussed.


Assuntos
Cloroquina/uso terapêutico , Terapia Genética , Hidroxicloroquina/uso terapêutico , Doenças Retinianas/terapia , Viroses/tratamento farmacológico , Animais , Betacoronavirus/efeitos dos fármacos , Cloroquina/farmacologia , Dependovirus/genética , Humanos , Hidroxicloroquina/farmacologia , Imunomodulação/efeitos dos fármacos , Doenças Retinianas/patologia
2.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32611687

RESUMO

The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.


Assuntos
Imunossupressores/uso terapêutico , Neoplasias/complicações , Viroses/terapia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/terapia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Hepatite C/terapia , Humanos , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Influenza Humana/terapia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Viroses/complicações , Viroses/tratamento farmacológico , Viroses/imunologia
3.
Int J Mol Sci ; 21(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521619

RESUMO

Viruses use cell machinery to replicate their genome and produce viral proteins. For this reason, several intracellular factors, including the redox state, might directly or indirectly affect the progression and outcome of viral infection. In physiological conditions, the redox balance between oxidant and antioxidant species is maintained by enzymatic and non-enzymatic systems, and it finely regulates several cell functions. Different viruses break this equilibrium and induce an oxidative stress that in turn facilitates specific steps of the virus lifecycle and activates an inflammatory response. In this context, many studies highlighted the importance of redox-sensitive pathways as novel cell-based targets for therapies aimed at blocking both viral replication and virus-induced inflammation. In the review, we discuss the most recent findings in this field. In particular, we describe the effects of natural or synthetic redox-modulating molecules in inhibiting DNA or RNA virus replication as well as inflammatory pathways. The importance of the antioxidant transcription factor Nrf2 is also discussed. Most of the data reported here are on influenza virus infection. We believe that this approach could be usefully applied to fight other acute respiratory viral infections characterized by a strong inflammatory response, like COVID-19.


Assuntos
Antivirais/uso terapêutico , Oxirredução/efeitos dos fármacos , Viroses/tratamento farmacológico , Animais , Infecções por Coronavirus/tratamento farmacológico , Glutationa/metabolismo , Humanos , Inflamação/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Viroses/imunologia , Viroses/patologia , Replicação Viral/efeitos dos fármacos
5.
Pharmacol Res ; 157: 104849, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360482

RESUMO

Taking anti-inflammatory drugs, including non-steroidal (NSAIDs), during Covid-19 infection, how much is risky? The French Minister of Health, who has raised an alarm on a possible risk deriving from the use of ibuprofen for the control of fever and other symptoms during the disease, opened the debate a few days ago. In this paper we examine available evidence from preclinical and clinical studies that had analysed the role of COX in the inflammatory process and the effects of NSAIDs in patients with infections. Most of the published studies that suggested not protective effects of NSAIDs were mainly performed in vitro or on animals. Therefore, their meaning in humans is to be considered with great caution. Based also on data suggesting protective effects of NSAIDs, we concluded that currently there is no evidence suggesting a correlation between NSAIDs and a worsening of infections. Further studies will be certainly needed to better define the role of NSAIDs and particularly COX2 inhibitors in patients with infections. In the meantime, we must wait for results of the revision started by the PRAC on May 2019 on the association ibuprofen/ketoprofen​​​​​​ and worsening of infections. Since nowadays no scientific evidence establishes a correlation between NSAIDS and worsening of COVID-19, patients should be advice against any NSAIDs self-medication when COVID-19 like symptoms are present.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Viroses/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Humanos , Pandemias
6.
Viruses ; 12(4)2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32272550

RESUMO

In the midst of the SARS-CoV-2/Covid-19 outbreak the need for research into, and development of, antiviral agents is brought into sharp focus worldwide for scientists, governments and the public alike [...].


Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Farmacorresistência Viral , Viroses/tratamento farmacológico , Animais , Humanos , Viroses/virologia
7.
J Integr Med ; 18(2): 152-158, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32113846

RESUMO

OBJECTIVE: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. METHODS: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. RESULTS: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. CONCLUSION: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Infecções Respiratórias/tratamento farmacológico , Viroses/tratamento farmacológico
8.
Int J Infect Dis ; 93: 268-276, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32081774

RESUMO

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.


Assuntos
Antivirais , Desenvolvimento de Medicamentos , Descoberta de Drogas , Animais , Antivirais/uso terapêutico , Humanos , Viroses/tratamento farmacológico
9.
BMC Infect Dis ; 20(1): 89, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000695

RESUMO

BACKGROUND: Outbreaks of acute undifferentiated febrile illness (AUFI) are common in Nepal, but the exact etiology or risk factors for them often go unrecognized. Diseases like influenza, enteric fever and rickettsial fevers account for majority of such outbreaks. Optimal diagnostic tests to inform treatment decisions are not available at the point-of-care. A proper epidemiological and clinical characterization of such outbreaks is important for appropriate treatment and control efforts. METHODS: An investigation was initiated as a response to increased presentation of patients at Patan Hospital from Chalnakhel locality in Dakchinkali municipality, Kathmandu with AUFI from June 10 to July 1, 2016. Focused group discussion with local inhabitants and the epidemiological curve of febrile patients at local primary health care centre confirmed the outbreak. The household-survey was conducted in the area with questionnaire administered on patients to characterize their illnesses and their medical records were reviewed. A different set of questionnaire was administered on the patients and controls to investigate the association with common risk factors. Water samples were collected and analyzed microbiologically. RESULTS: Eighty one patients from 137 households suffered from febrile illness within 6 weeks window before the investigation. All the 67 sampled patients with acute fever had a generalized illness without a discernible focus of infection. Only 38% of the patients had received a clinical diagnosis while the rest were treated empirically without a diagnosis. Three patients had blood culture confirmed enteric fever. Forty-two (63%) patients had been administered antibiotics, most commonly, ofloxacin, cefixime or azithromycin with a mean fever clearance time of 4 days. There was no definite association between several risk factors and fever. Fecal contamination was noted in tap water samples. CONCLUSION: Based on the pattern of illness, this outbreak was most likely a mixture of self-limiting viral infections and enteric fever. This study shows that even in the absence of a confirmed diagnosis, a detailed characterization of the illness at presentation and the recovery course can suggest the diagnosis and help in formulating appropriate recommendation for treatment and control.


Assuntos
Antibacterianos/uso terapêutico , Febre/epidemiologia , Febre/etiologia , Febre Tifoide/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , Cefixima/uso terapêutico , Criança , Surtos de Doenças , Feminino , Febre/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Ofloxacino/uso terapêutico , Fatores de Risco , Febre Tifoide/tratamento farmacológico , Febre Tifoide/etiologia , Viroses/tratamento farmacológico , Viroses/epidemiologia , Viroses/etiologia , Adulto Jovem
10.
Orv Hetil ; 161(2): 50-55, 2020 Jan.
Artigo em Húngaro | MEDLINE | ID: mdl-31902236

RESUMO

Introduction: Exudative tonsillitis is a common clinical picture during childhood. The majority of these cases are caused by viruses (Epstein-Barr virus [EBV], cytomegalovirus [CMV], influenza virus, parainfluenza virus, and adenovirus), and only some infections are caused by bacteria, mainly group A streptococci (GAS). On the basis of international guidelines, routine use of early antibiotic treatment is not recommended in these cases, because it seems not to prevent GAS-associated complications. Aim: Our aim was to determine those laboratory results which are useful to distinguish between bacterial and viral infections in children with exudative tonsillitis to reduce antibiotic overuse. Method: In our study, we evaluated 135 clinical data from 133 children with exudative tonsillitis. Patients were grouped according to the following criteria: the first group contained patients with acute CMV or EBV infections, while in the second group, CMV or EBV infections were not confirmed using serology. Results: On the basis of our results, EBV or CMV infections (66/135, 48.8%) were serologically confirmed in the majority of cases with exudative tonsillitis between 2016 and 2017, while the causative role of GAS was minimal in this patient group (3/65, 4.61%). In spite of this finding, the majority of patients (92%) were treated with antibiotics. Conclusion: Our retrospective findings confirmed that it is not possible to determine the causative agent of this clinical picture on the basis of symptoms, and physical findings, moreover laboratory results, such as high white blood cell count could not confirm bacterial infection. At the same time, elevated transaminase levels may refer to viral origin of infection, especially EBV or CMV with high predictive value; the use of extended laboratory tests may reduce the unnecessary antibiotic consumption. Orv Hetil. 2020; 161(2): 50-55.


Assuntos
Infecções Estreptocócicas/etiologia , Tonsilite/etiologia , Viroses/etiologia , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/análise , Anticorpos Antivirais/análise , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Criança , Humanos , Faringe/microbiologia , Faringe/virologia , Estudos Retrospectivos , Tonsilite/tratamento farmacológico , Viroses/diagnóstico , Viroses/tratamento farmacológico
11.
Adv Exp Med Biol ; 1217: 99-110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31898224

RESUMO

Cullin-RING ubiquitin ligases (CRLs) are efficient and diverse toolsets of the cells to regulate almost every biological process. However, these characteristics have also been usurped by many viruses to optimize for their replication. CRLs are often at the forefront of the arms races in the coevolution of viruses and hosts. Here we review the modes of actions and functional consequences of viral manipulations of host cell CRLs. We also discuss the therapeutic applications to target these viral manipulations for treating viral infections.


Assuntos
Proteínas Culina/metabolismo , Interações Hospedeiro-Patógeno , Viroses/metabolismo , Viroses/virologia , Vírus/metabolismo , Evolução Biológica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Viroses/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Vírus/efeitos dos fármacos , Vírus/crescimento & desenvolvimento
12.
Am J Respir Crit Care Med ; 201(1): 83-94, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31461630

RESUMO

Rationale: Viral infections are major drivers of exacerbations and clinical burden in patients with asthma and chronic obstructive pulmonary disease (COPD). IFN-ß is a key component of the innate immune response to viral infection. To date, studies of inhaled IFN-ß treatment have not demonstrated a significant effect on asthma exacerbations.Objectives: The dynamics of exogenous IFN-ß activity were investigated to inform on future clinical indications for this potential antiviral therapy.Methods: Monocyte-derived macrophages (MDMs), alveolar macrophages, and primary bronchial epithelial cells (PBECs) were isolated from healthy control subjects and patients with COPD and infected with influenza virus either prior to or after IFN-ß stimulation. Infection levels were measured by the percentage of nucleoprotein 1-positive cells using flow cytometry. Viral RNA shedding and IFN-stimulated gene expression were measured by quantitative PCR. Production of inflammatory cytokines was measured using MSD.Measurements and Main Results: Adding IFN-ß to MDMs, alveolar macrophages, and PBECs prior to, but not after, infection reduced the percentage of nucleoprotein 1-positive cells by 85, 56, and 66%, respectively (P < 0.05). Inhibition of infection lasted for 24 hours after removal of IFN-ß and was maintained albeit reduced up to 1 week in MDMs and 72 hours in PBECs; this was similar between healthy control subjects and patients with COPD. IFN-ß did not induce inflammatory cytokine production by MDMs or PBECs but reduced influenza-induced IL-1ß production by PBECs.Conclusions: In vitro modeling of IFN-ß dynamics highlights the potential for intermittent prophylactic doses of exogenous IFN-ß to modulate viral infection. This provides important insights to aid the future design of clinical trials of IFN-ß in asthma and COPD.


Assuntos
Antivirais/uso terapêutico , Asma/tratamento farmacológico , Interferon beta/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Viroses/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/imunologia , Asma/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/virologia , Viroses/imunologia
13.
Phytother Res ; 34(4): 742-768, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31858645

RESUMO

Viral infections represent one of the main causes of disease worldwide, especially today due to the increase of migration, global travel, and urbanization. The several side effects of the conventional drugs and the growing phenomenon of resistance have led researchers to turn to the plant kingdom as a source of potential new antiviral drugs. The aim of this work is to summarize the updated evidence for antiviral activity of different plants and their isolated bioactive compounds, evaluating also the potential interactions, which can occur in cotreatment with conventional antiviral drugs. The plant complexes have proved to be usually more active than their most abundant isolated compounds by hypothesizing synergistic mechanisms. In addition to cellular and molecular investigations, molecular docking studies have proved essential in highlighting the interaction mechanisms of bioactive compounds with target molecules. However, the use of nonstandardized extracts, or too high concentrations in vitro, which do not reproduce their bioavailability in vivo, are often limiting factors. Moreover, the lack of studies concerning the safety profile of plant extracts and their isolated compounds, alone or in combination with conventional antiviral drugs, is the most worrying aspect. In light of this, further studies are needed to validate their possible therapeutic use.


Assuntos
Antivirais/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Viroses/tratamento farmacológico , Animais , Antivirais/química , Humanos , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química
14.
Rev Med Suisse ; 15(666): 1825-1830, 2019 Oct 09.
Artigo em Francês | MEDLINE | ID: mdl-31599524

RESUMO

Viral infections are extremely common and generally self-restricted, thus antiviral therapy is limited to precise indications. Apart from HIV (not reviewed in this article), the principal treatable viruses are HSV 1 and 2, VZV, CMV, Influenza A and B, and hepatitis B and C. Vaccination is another cornerstone of viral infections control. This article summarizes actual and available therapy. New treatments arrived recently on the market or are being developed : HCV can now be treated with a high success rate, baloxavir against the flu, a new zoster vaccine will probably soon be available in Switzerland and letermovir improves CMV prophylaxis in the case of hematopoietic stem cell transplant.


Assuntos
Antivirais/uso terapêutico , Medicina Geral , Viroses/tratamento farmacológico , Clínicos Gerais , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Suíça , Vacinas Virais/provisão & distribução , Viroses/prevenção & controle , Viroses/virologia
15.
Curr Pharm Biotechnol ; 20(13): 1108-1121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31400263

RESUMO

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunoterapia/métodos , Viroses/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Humanos , Viroses/virologia
16.
Photochem Photobiol Sci ; 18(11): 2565-2612, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397467

RESUMO

Photodynamic therapy (PDT) is a well-established treatment option in the treatment of certain cancerous and pre-cancerous lesions. Though best-known for its application in tumor therapy, historically the photodynamic effect was first demonstrated against bacteria at the beginning of the 20th century. Today, in light of spreading antibiotic resistance and the rise of new infections, this photodynamic inactivation (PDI) of microbes, such as bacteria, fungi, and viruses, is gaining considerable attention. This review focuses on the PDI of viruses as an alternative treatment in antiviral therapy, but also as a means of viral decontamination, covering mainly the literature of the last decade. The PDI of viruses shares the general action mechanism of photodynamic applications: the irradiation of a dye with light and the subsequent generation of reactive oxygen species (ROS) which are the effective phototoxic agents damaging virus targets by reacting with viral nucleic acids, lipids and proteins. Interestingly, a light-independent antiviral activity has also been found for some of these dyes. This review covers the compound classes employed in the PDI of viruses and their various areas of use. In the medical area, currently two fields stand out in which the PDI of viruses has found broader application: the purification of blood products and the treatment of human papilloma virus manifestations. However, the PDI of viruses has also found interest in such diverse areas as water and surface decontamination, and biosafety.


Assuntos
Luz , Fotoquimioterapia/tendências , Viroses/terapia , Vírus/efeitos da radiação , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Viroses/tratamento farmacológico , Viroses/metabolismo , Vírus/efeitos dos fármacos , Vírus/metabolismo
18.
Expert Opin Drug Discov ; 14(11): 1103-1112, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31364421

RESUMO

Introduction: Monoclonal antibody-based therapies now represent the single-largest class of molecules undergoing clinical investigation. Although a handful of different monoclonal antibodies have been clinically approved for bacterial and viral indications, including rabies, therapies based on monoclonal antibodies are yet to fully enter the fields of neglected tropical diseases and other infectious diseases. Areas covered: This review presents the current state-of-the-art in the development and use of monoclonal antibodies against neglected tropical diseases and other infectious diseases, including viral, bacterial, and parasitic infections, as well as envenomings by animal bites and stings. Additionally, a short section on mushroom poisonings is included. Key challenges for developing antibody-based therapeutics are discussed for each of these fields. Expert opinion: Neglected tropical diseases and other infectious diseases represent a golden opportunity for academics and technology developers for advancing our scientific capabilities within the understanding and design of antibody cross-reactivity, use of oligoclonal antibody mixtures for multi-target neutralization, novel immunization methodologies, targeting of evasive pathogens, and development of fundamentally novel therapeutic mechanisms of action. Furthermore, a huge humanitarian and societal impact is to gain by exploiting antibody technologies for the development of biotherapies against diseases, for which current treatment options are suboptimal or non-existent.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Desenvolvimento de Medicamentos/métodos , Doenças Negligenciadas/tratamento farmacológico , Animais , Anticorpos Monoclonais/farmacologia , Infecções Bacterianas/tratamento farmacológico , Humanos , Doenças Parasitárias/tratamento farmacológico , Medicina Tropical , Viroses/tratamento farmacológico
19.
Clin Sci (Lond) ; 133(14): 1663-1703, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31346069

RESUMO

Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial-host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen-host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.


Assuntos
Moléculas de Adesão Celular/imunologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/imunologia , Animais , Antibacterianos/administração & dosagem , Antivirais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/etiologia , Moléculas de Adesão Celular/genética , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/genética , Viroses/tratamento farmacológico , Viroses/etiologia
20.
J Fish Dis ; 42(10): 1383-1389, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31322740

RESUMO

Tilapia lake virus (TiLV) is an emerging virus associated with high fish mortality and economic losses. This study investigates the virucidal effects of the following disinfectants (active ingredients) on TiLV: 2.5 ppm iodine, 10 ppm sodium hypochlorite (NaOCl), 300 ppm hydrogen peroxide (H2 O2 ), 80 ppm formalin and 5,000 ppm (0.5%) Virkon® . Factors that affect the disinfectants' efficacy, including temperature, contact time and soiling (organic matter) interference, were examined under conditions mimicking natural aquaculture practices. TiLV inactivation of higher than 5 log10 TCID50  ml-1 was achieved after 10 min and at 28°C for all disinfectants except formalin; similar inactivation levels were reached by NaOCl and Virkon® at 10 min and 4°C. Extended exposure to formalin from 10 to 60 min at 28°C rendered more than 5 log10 inactivation. Increasing synthetic organic matter in the water to mimic soiling interference reduced the efficacy of NaOCl, iodine and H2 O2 when tested at 10 min and 28°C; however, Virkon® still achieved more than 5 log10 inactivation. This study demonstrates that most common disinfectants effectively reduced viral loads to minimum levels. To limit the spread of TiLV in aquaculture farms and related facilities, the appropriate use of such disinfectants should therefore be promoted and implemented.


Assuntos
Desinfetantes/farmacologia , Doenças dos Peixes/tratamento farmacológico , Tilápia , Viroses/veterinária , Inativação de Vírus , Animais , Doenças dos Peixes/virologia , Especificidade da Espécie , Viroses/tratamento farmacológico , Viroses/virologia , Vírus/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA