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1.
Curr Opin HIV AIDS ; 15(6): 336-340, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33002954

RESUMO

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is a highly contagious and potentially lethal pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No specific antiviral treatment is currently available. The purpose of this review is to highlight the main repurposed drug treatments with in-vitro or in-vivo efficacy against the SARS-CoV-2. RECENT FINDINGS: Recent clinical trials suggested remdesivir, IFN-ß-1b and favipiravir have potential clinical and/or virological benefits on patients with COVID-19. Short course of stress dose of corticosteroids might be used as adjunctive treatment to patients who are late presenters with cytokine storm. Convalescent plasma from recovered COVID-19 patients with high neutralizing antibody might also be beneficial in the treatment of severe disease. SUMMARY: Early effective antiviral therapy in COVID-19 patients will suppress the SARS-CoV-2 viral load. Adjunctive therapy with corticosteroid and convalescent plasma might further ameliorate the cytokine response. Further randomized clinical trials of combination therapy are needed.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Humanos , Imunização Passiva , Interferon beta/uso terapêutico , Pandemias , Pneumonia Viral/imunologia
2.
Nat Rev Immunol ; 20(10): 585-586, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788708
3.
Brasília; s.n; 6 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117629

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 17 artigos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , gama-Globulinas/uso terapêutico , Imunoglobulinas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Vacinas/uso terapêutico , Cloroquina/uso terapêutico , Interferon beta/uso terapêutico , Aldeído Redutase/antagonistas & inibidores , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Sulfato de Zinco/uso terapêutico , Ritonavir/uso terapêutico , Oseltamivir/uso terapêutico , Lopinavir/uso terapêutico , Hidroxicloroquina/uso terapêutico
5.
Cytokine Growth Factor Rev ; 54: 43-50, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32665127

RESUMO

Coronavirus disease 2019 (COVID-19) first emerged in late 2019 in China. At the time of writing, its causative agent SARS-CoV-2 has spread worldwide infecting over 9 million individuals and causing more than 460,000 deaths. In the absence of vaccines, we are facing the dramatic challenge of controlling COVID-19 pandemic. Among currently available drugs, type I Interferons (IFN-I) - mainly IFN-α and ß -represent ideal candidates given their direct and immune-mediated antiviral effects and the long record of clinical use. However, the best modalities of using these cytokines in SARS-CoV-2 infected patients is a matter of debate. Here, we discuss how we can exploit the current knowledge on IFN-I system to tailor the most promising dosing, timing and route of administration of IFN-I to the disease stage, with the final aim of making these cytokines a valuable therapeutic strategy in today's fight against COVID-19 pandemic.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/prevenção & controle , Interferon-alfa/uso terapêutico , Interferon beta/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Humanos , Imunoterapia/métodos , Prevenção Secundária/métodos
6.
Mult Scler Relat Disord ; 42: 102196, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32480326

RESUMO

BACKGROUND: The Coronavirus (COVID-19), (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has been spreading worldwide since its first identification in China. It has been speculated that patients with comorbidities and elderly patients could be at high risk for the pandemic reasoned respiratory insufficiency and death. At first, it was thought that the patients who use immunmodulator therapy could be even at higher risks of disease complications. However, it has been also speculated about that using immunmodulators could be an advantage for the clinical prognosis. Therefore, several immunmodulators are currently being tested as potential treatment for COVID-19. METHODS: In this paper we report on a patient that has been treated with type 1 interferon for multiple sclerosis who developed COVID-19. RESULTS: Despite using immunmodulator, the symptoms of the patient at hospitalization were mild and he did not show elevated D-dimer, and there was no lymphopenia. He was discharged to home-quarantine with no symptoms. DISCUSSION: This report supports the idea of using type 1 interferon in the treatment could be effective in COVID-19 affected patients.


Assuntos
Infecções por Coronavirus/fisiopatologia , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Adulto , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Tosse/etiologia , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação , Masculino , Esclerose Múltipla/complicações , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/tratamento farmacológico , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
8.
Mult Scler Relat Disord ; 43: 102174, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464584

RESUMO

BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.


Assuntos
Betacoronavirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Imunossupressores/uso terapêutico , Linfopenia/imunologia , Esclerose Múltipla/terapia , Pneumonia Viral/imunologia , Alemtuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antivirais/imunologia , Cladribina/uso terapêutico , Crotonatos/uso terapêutico , Desprescrições , Fumarato de Dimetilo/uso terapêutico , Cloridrato de Fingolimode/uso terapêutico , Acetato de Glatiramer/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Evasão da Resposta Imune/imunologia , Imunidade Inata/imunologia , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Macrófagos/imunologia , Monócitos/imunologia , Natalizumab/uso terapêutico , Pandemias , Síndrome do Desconforto Respiratório do Adulto/imunologia , Toluidinas/uso terapêutico
9.
Neurology ; 94(22): e2373-e2383, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32430312

RESUMO

OBJECTIVE: Disease-modifying treatments (DMTs) are the gold standard for slowing disability progression in multiple sclerosis (MS), but their effects on cognitive impairment, a key symptom of the disease, are mostly unknown. We conducted a systematic review and meta-analysis to evaluate the differential effects of DMTs on cognitive test performance in relapsing-remitting MS (RRMS). METHODS: PubMed, Scopus, and Cochrane Library were searched for studies reporting longitudinal cognitive performance data related to all major DMTs. The standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used as the main effect size measure. RESULTS: Forty-four studies, including 55 distinct MS patient samples, were found eligible for the systematic review. Twenty-five studies were related to platform therapies (mainly ß-interferon [n = 17] and glatiramer acetate [n = 4]), whereas 22 studies were related to escalation therapies (mainly natalizumab [n = 14] and fingolimod [n = 6]). Reported data were mostly confined to the cognitive domain processing speed. A meta-analysis including 41 studies and 7,131 patients revealed a small to moderate positive effect on cognitive test performance of DMTs in general (g = 0.27, 95% confidence interval [CI] = [0.21-0.33]), but no statistically significant differences between platform (g = 0.27, 95% CI = [0.18-0.35]) and escalation therapies (g = 0.28, 95% CI = [0.19-0.37]) or between any single DMT and ß-interferon. CONCLUSIONS: DMTs are effective in improving cognitive test performance in RRMS, but a treatment escalation mainly to amend cognition is not supported by the current evidence. Given the multitude of DMTs and their widespread use, the available data regarding differential treatment effects on cognitive impairment are remarkably scant. Clinical drug trials that use more extensive cognitive outcome measures are urgently needed.


Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Cognição/fisiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Cloridrato de Fingolimode/farmacologia , Cloridrato de Fingolimode/uso terapêutico , Acetato de Glatiramer/farmacologia , Acetato de Glatiramer/uso terapêutico , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Imunossupressores/farmacologia , Interferon beta/farmacologia , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Natalizumab/farmacologia , Natalizumab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
10.
Drug Discov Ther ; 14(2): 67-72, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: covidwho-116944

RESUMO

The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus , Cloroquina/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/tratamento farmacológico , Darunavir/uso terapêutico , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferon-alfa/uso terapêutico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Pandemias , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico
11.
Drug Discov Ther ; 14(2): 67-72, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32336723

RESUMO

The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus , Cloroquina/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/tratamento farmacológico , Darunavir/uso terapêutico , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferon-alfa/uso terapêutico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Pandemias , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico
12.
Artigo em Inglês | MEDLINE | ID: covidwho-5693

RESUMO

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-ß) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-ß also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-ß against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ensaios Clínicos como Assunto , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Humanos , Imunização Passiva , Interferon beta/uso terapêutico , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Ribavirina/uso terapêutico , Vírus da SARS/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores
13.
Artigo em Inglês | MEDLINE | ID: mdl-32152082

RESUMO

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-ß) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-ß also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-ß against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Ensaios Clínicos como Assunto , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Humanos , Imunização Passiva , Interferon beta/uso terapêutico , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Ribavirina/uso terapêutico , Vírus da SARS/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores
14.
Georgian Med News ; (298): 84-88, 2020 Jan.
Artigo em Russo | MEDLINE | ID: mdl-32141856

RESUMO

About 30-40% of multiple sclerosis (MS) patients treated with interferon-beta (IFN-ß) develop neutralizing antibodies (NABs) to IFN-ß. NABs reduce bioavailability of IFN-ß, which leads to a decrease in the therapy effectiveness. The introduction of IFN-ß induce production of several proteins, which are used as markers of the therapy effectiveness. In this study, we assessed the prognostic significance of MS activity biomarkers in relation to the clinical data of MS patients treated with IFN-ß. The study involved 30 MS patients receiving IFN-ß. The average duration of therapy was 3.5 (3.4-5.3) years. The study showed the prevalence of NAbs formation in MS patients was 13% of cases, a year later - 30%. The level of viperin in patients without exacerbations during the observation period was lower than in patients with exacerbations. The study revealed the prognostic significance of viperin in relation to the frequency of exacerbations: viperin concentration above 0.2 ng / ml is a risk factor for exacerbation of MS. The results of this study suggest that viperin concentration in the serum could be used a prognostic marker in MS patients treated with interferons.


Assuntos
Interferon beta/farmacologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Anticorpos/análise , Anticorpos/sangue , Anticorpos Neutralizantes , Biomarcadores/análise , Biomarcadores/sangue , República da Geórgia/epidemiologia , Humanos , Interferon beta/efeitos adversos , Interferon beta/uso terapêutico , Esclerose Múltipla/sangue , Esclerose Múltipla/epidemiologia , Prevalência , Prognóstico , Resultado do Tratamento
15.
Virology ; 541: 160-173, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32056714

RESUMO

Unique among human viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes several homologs of cellular interferon regulatory factors (vIRFs). Since KSHV expresses multiple factors that can inhibit interferon (IFN) signaling to promote virus production, it is still unclear to what extent vIRFs contribute to these specific processes during KSHV infection. To study the function of vIRFs during viral infection, we engineered 3xFLAG-tagged-vIRF and vIRF-knockout recombinant KSHV clones, which were utilized to test vIRF expression, as well as their requirement for viral replication, virus production, and inhibition of the type I IFN pathway in different models of lytic KSHV infection. Our data show that all vIRFs can be expressed as lytic viral proteins, yet were dispensable for KSHV production and inhibition of type I IFN. Nevertheless, as vIRFs were able to suppress IFN-stimulated antiviral genes, vIRFs may still promote the KSHV lytic cycle in the presence of an ongoing antiviral response.


Assuntos
Herpesvirus Humano 8/fisiologia , Fatores Reguladores de Interferon/fisiologia , Interferon Tipo I/antagonistas & inibidores , Proteínas Virais/fisiologia , Replicação Viral , Células Cultivadas , Humanos , Interferon Tipo I/biossíntese , Interferon beta/genética , Interferon beta/uso terapêutico , Transdução de Sinais/fisiologia , Ativação Viral
16.
Nat Commun ; 11(1): 222, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: covidwho-326513

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus/tratamento farmacológico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Ritonavir/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Animais , Antivirais/uso terapêutico , Carboxilesterase/genética , Infecções por Coronavirus/patologia , Combinação de Medicamentos , Desenvolvimento de Medicamentos , Feminino , Humanos , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Knockout , Carga Viral , Replicação Viral/efeitos dos fármacos
17.
Nat Commun ; 11(1): 222, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924756

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus/tratamento farmacológico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Ritonavir/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Animais , Antivirais/uso terapêutico , Carboxilesterase/genética , Infecções por Coronavirus/patologia , Combinação de Medicamentos , Desenvolvimento de Medicamentos , Feminino , Humanos , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Knockout , Carga Viral , Replicação Viral/efeitos dos fármacos
18.
J Biomed Sci ; 27(1): 4, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898495

RESUMO

Dengue virus (DENV) is the etiological agent of dengue fever. Severe dengue could be fatal and there is currently no effective antiviral agent or vaccine. The only licensed vaccine, Dengvaxia, has low efficacy against serotypes 1 and 2. Cellular miRNAs are post-transcriptional regulators that could play a role in direct regulation of viral genes. Host miRNA expressions could either promote or repress viral replications. Induction of some cellular miRNAs could help the virus to evade the host immune response by suppressing the IFN-α/ß signaling pathway while others could upregulate IFN-α/ß production and inhibit the viral infection. Understanding miRNA expressions and functions during dengue infections would provide insights into the development of miRNA-based therapeutics which could be strategized to act either as miRNA antagonists or miRNA mimics. The known mechanisms of how miRNAs impact DENV replication are diverse. They could suppress DENV multiplication by directly binding to the viral genome, resulting in translational repression. Other miRNA actions include modulation of host factors. In addition, miRNAs that could modulate immunopathogenesis are discussed. Major hurdles lie in the development of chemical modifications and delivery systems for in vivo delivery. Nevertheless, advancement in miRNA formulations and delivery systems hold great promise for the therapeutic potential of miRNA-based therapy, as supported by Miravirsen for treatment of Hepatitis C infection which has successfully completed phase II clinical trial.


Assuntos
Dengue/tratamento farmacológico , Interferon-alfa/genética , Interferon beta/genética , MicroRNAs/genética , Antivirais , Dengue/genética , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/patogenicidade , Humanos , Imunidade Inata/genética , Interferon-alfa/uso terapêutico , Interferon beta/uso terapêutico , MicroRNAs/uso terapêutico , Transdução de Sinais/genética , Replicação Viral/genética
19.
J Neurol Neurosurg Psychiatry ; 91(3): 271-277, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31974130

RESUMO

OBJECTIVE: This study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability. METHODS: We retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called 'MAGNIMS score' (low: no relapses and <3 new T2 lesions; medium: no relapses and ≥3 new T2 lesions or 1 relapse and 0-2 new T2 lesions; high: 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs). RESULTS: At follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, p<0.001) after the first year of treatment. In the low score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment. CONCLUSIONS: Early marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.


Assuntos
Esclerose Múltipla Recidivante-Remitente/diagnóstico , Adulto , Progressão da Doença , Feminino , Acetato de Glatiramer/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
20.
Medicina (Kaunas) ; 56(2)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973138

RESUMO

Pregnancy rates are rapidly increasing among women of reproductive age diagnosed with multiple sclerosis (MS). Through pre-conception, pregnancy and post-partum periods, there is a need for disease control management, to decrease chances of MS relapses while avoiding potential risks to the mother and the fetus. However, pregnancy is not always compatible with the available highly effective MS treatments. This narrative review provides the aspects of pregnancy's outcomes and the impact on disease activity, choices of anesthesia and the management of relapses during the pregnancy and breastfeeding period. Available disease modifying treatment is discussed in the article with new data supporting the strategy of continuing natalizumab after conception, as it is related to a decreased risk of MS relapses during the pregnancy and postpartum period.


Assuntos
Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Adulto , Alemtuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Crotonatos/uso terapêutico , Fumarato de Dimetilo/uso terapêutico , Feminino , Cloridrato de Fingolimode/uso terapêutico , Acetato de Glatiramer/uso terapêutico , Humanos , Interferon beta/uso terapêutico , Esclerose Múltipla/epidemiologia , Natalizumab/uso terapêutico , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Resultado da Gravidez/epidemiologia , Estudos Prospectivos , Rituximab/uso terapêutico , Toluidinas/uso terapêutico
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