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1.
Cells ; 10(2)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525562

RESUMO

Lithium salts have been in the therapeutic toolbox for better or worse since the 19th century, with purported benefit in gout, hangover, insomnia, and early suggestions that lithium improved psychiatric disorders. However, the remarkable effects of lithium reported by John Cade and subsequently by Mogens Schou revolutionized the treatment of bipolar disorder. The known molecular targets of lithium are surprisingly few and include the signaling kinase glycogen synthase kinase-3 (GSK-3), a group of structurally related phosphomonoesterases that includes inositol monophosphatases, and phosphoglucomutase. Here we present a brief history of the therapeutic uses of lithium and then focus on GSK-3 as a therapeutic target in diverse diseases, including bipolar disorder, cancer, and coronavirus infections.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Animais , Antimaníacos/farmacologia , Transtorno Bipolar/metabolismo , Coronavirus/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Compostos de Lítio/farmacologia , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
FASEB J ; 35(2): e21245, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33495994

RESUMO

Lymphopenia is commonly observed in SARS and COVID-19 patients although the lymphocyte count is not always below 0.8 × 109 /L in all the patients. It is suggested that lymphopenia serves as a useful predictor for prognosis in the patients. It is also hypothesized that lymphopenia is related to glucocorticoids and apoptosis. However, the ordering between lymphopenia and apoptosis appears different between SARS and COVID-19 patients, ie, lymphopenia is prior to apoptosis in SARS patients whereas apoptosis is prior to lymphopenia in COVID-19 patients. This paper attempts to figure out this contradiction through three players, lymphopenia, glucocorticoids, and apoptosis. Although the literature does not provide a solid explanation, the level of glucocorticoids could determine the ordering between lymphopenia and apoptosis because the administration of high doses of glucocorticoids could lead to lymphopenia whereas low doses of glucocorticoids could benefit patients. In the meantime, this paper raises several questions, which need to be answered in order to better understand the whole course of COVID-19.


Assuntos
Glucocorticoides , Linfopenia , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave , Apoptose/efeitos dos fármacos , /tratamento farmacológico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Linfopenia/tratamento farmacológico , Linfopenia/etiologia , Linfopenia/metabolismo , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/metabolismo
3.
Med. clín (Ed. impr.) ; 156(1): 7-12, ene. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-196134

RESUMO

OBJETIVO: Analizar si existe asociación entre el uso de glucocorticoides a dosis altas y la evolución de la SAFI (saturación/fracción inspirada de oxígeno) o el tiempo hasta el alta, en pacientes hospitalizados por COVID-19. MÉTODOS: Estudio observacional sobre una cohorte de 418 pacientes ingresados en 3 hospitales comarcales de Cataluña (España). Como resultados primarios se estudiaron la evolución de la SAFI en las primeras 48h de tratamiento y el tiempo hasta el alta. Los resultados se compararon entre pacientes tratados y no tratados con glucocorticoides (metilprednisolona 1-2mg/kg/día o dexametasona 20-40mg/día), mediante el análisis de subcohortes emparejadas por múltiples factores clínicos y pronósticos, así como mediante modelos multivariantes de Cox, ajustados por diversos factores pronósticos. El uso simultáneo de diferentes tratamientos para la COVID-19 fue tenido en cuenta, tanto en el emparejamiento de subcohortes como en la regresión de Cox. RESULTADOS: Hubo 187 pacientes con glucocorticoides; de ellos, 25 pacientes pudieron ser emparejados con un número equivalente de pacientes control. En las subcohortes emparejadas, no se apreció diferencia en el tiempo hasta el alta (log-rank: p = 0,291), ni en el cambio en la SAFI a las 48h desde la basal (glucocorticoides: −0,04; controles: +0,37; p = 0,095). Los modelos multivariantes mediante regresión de Cox mostraron un tiempo hasta el alta significativamente más largo en pacientes tratados con glucocorticoides (hazard ratio: 7,26; IC 95%: 3,30-15,95). CONCLUSIONES: No hemos encontrado mejoría en la función respiratoria o tiempo hasta el alta, asociado al uso de glucocorticoides a dosis altas


OBJECTIVE: To analyze whether there is an association between the use glucocorticoids at high doses, and the evolution of saturation/fraction of inspired oxygen (SAFI) or time to discharge, in patients hospitalized with COVID-19. METHODS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI in the first 48hours of treatment and the time to discharge. The results were compared between patients treated and untreated with glucocorticoids (methylprednisolone 1-2mg/kg/day o dexamethasone 20-40mg/day) through sub-cohort analyses matched for multiple clinical and prognostic factors, as well as through Cox multivariate models adjusted for prognostic factors. The simultaneous use of different treatments for COVID-19 was taken into account, both in sub-cohorts matching and in Cox regression. RESULTS: There were 187 patients treated with glucocorticoids; of these, 25 patients could be matched with an equivalent number of control patients. In the analysis of these matched sub-cohorts, no significant difference was observed in time to discharge (log-rank: p = 0.291) or the increment in SAFI at 48hours of treatment (glucocorticoides: −0.04; controls: +0.37; p = 0.095). Multivariate models using Cox regression showed a significantly longer time to discharge in patients treated with glucocorticoids (hazard ratio: 7.26; 95% IC: 3.30-15.95). CONCLUSIONS: We have not found improvement in respiratory function or time until discharge, associated with the use of glucocorticoids at high doses


Assuntos
Humanos , Masculino , Feminino , Idoso , Glucocorticoides/administração & dosagem , Alta do Paciente , Estudos de Coortes , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Oxigênio/administração & dosagem , Metilprednisolona/administração & dosagem , Dexametasona/administração & dosagem , Síndrome Respiratória Aguda Grave/tratamento farmacológico
4.
Pharmacol Res Perspect ; 9(1): e00691, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33378565

RESUMO

Coronaviruses represent global health threat. In this century, they have already caused two epidemics and one serious pandemic. Although, at present, there are no approved drugs and therapies for the treatment and prevention of human coronaviruses, several agents, FDA-approved, and preclinical, have shown in vitro and/or in vivo antiviral activity. An in-depth analysis of the current situation leads to the identification of several potential drugs that could have an impact on the fight against coronaviruses infections. In this review, we discuss the virology of human coronaviruses highlighting the main biological targets and summarize the current state-of-the-art of possible therapeutic options to inhibit coronaviruses infections. We mostly focus on FDA-approved and preclinical drugs targeting viral conserved elements.


Assuntos
/metabolismo , Infecções por Coronavirus/metabolismo , Coronavirus/metabolismo , Dipeptidil Peptidase 4/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , /antagonistas & inibidores , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/metabolismo , Antivirais/administração & dosagem , Antivirais/metabolismo , Azóis/administração & dosagem , Azóis/metabolismo , Coronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/metabolismo , Humanos , Naftoquinonas/administração & dosagem , Naftoquinonas/metabolismo , Compostos Organosselênicos/administração & dosagem , Compostos Organosselênicos/metabolismo , Síndrome Respiratória Aguda Grave/tratamento farmacológico
5.
Int J Mol Sci ; 21(21)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138181

RESUMO

The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.


Assuntos
Lesão Pulmonar Aguda/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Vasoconstrição/fisiologia , Betacoronavirus , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Sistema Calicreína-Cinina/fisiologia , Pandemias , Sistema Renina-Angiotensina/fisiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vasoconstrição/efeitos dos fármacos
6.
Molecules ; 25(22)2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202656

RESUMO

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Betacoronavirus/patogenicidade , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/fisiopatologia , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Esquema de Medicação , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/virologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia , Zika virus/patogenicidade , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/virologia
7.
Med. clín (Ed. impr.) ; 155(10): 448-453, nov. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-191726

RESUMO

Actualmente no hay ningún fármaco aprobado para el tratamiento de la COVID-19. Se emplean fármacos de manera empírica según experiencia y disponibilidad, pero no existen estudios controlados que demuestren su eficacia y seguridad. En este contexto, es importante que los médicos dispongan de información de los posibles efectos adversos tanto inmunológicos como no inmunológicos de estos medicamentos. En esta revisión se repasa el fundamento para su uso en la infección por SARS-Cov-2, así como las reacciones adversas más frecuentes; no se trata de una revisión sistemática sino narrativa. Se han incluido aquellos fármacos que se utilizan con el fin de abordar adecuadamente las dos fases clínicas que parece tener la enfermedad en su manifestación más grave: una primera fase con predominio de infección viral y una segunda fase con predominio de una respuesta inflamatoria. También se han repasado los casos de reacciones a dichos fármacos recogidas en el Programa de Farmacovigilancia del hospital antes del inicio de la pandemia


Currently, there is no treatment approved for COVID-19. Numerous drugs are being used in an empirical manner according to experience and availability. Studies demonstrating their efficacy and safety are still to be published. Thus, it is of vital importance for healthcare workers to be well informed and updated regarding possible immunological and non-immunological adverse effects regarding such treatments. In this narrative revision, the rationale use of these treatments in the SARS-CoV-2 infection is emphasized as well as their most frequently described adverse drug reactions. Drugs that are being essayed to counteract both clinical phases that are thought to take place in the severe stage of this disease are included; an initial phase where a viral infection prevails and a second phase where an inflammatory response takes over. Adverse reactions registered in the Pharmacovigilance Program of our hospital before the onset of this pandemic have also been included


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Betacoronavirus/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/virologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Pandemias , Farmacovigilância
9.
Clin Microbiol Rev ; 34(1)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33055231

RESUMO

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Doença pelo Vírus Ebola/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/farmacologia , Alanina/farmacocinética , Alanina/farmacologia , Antivirais/farmacocinética , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo/métodos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Esquema de Medicação , Ebolavirus/efeitos dos fármacos , Ebolavirus/crescimento & desenvolvimento , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/patologia , Doença pelo Vírus Ebola/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/crescimento & desenvolvimento , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias , Segurança do Paciente , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/crescimento & desenvolvimento , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia , Análise de Sobrevida , Resultado do Tratamento
10.
Nutrients ; 12(11)2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33121019

RESUMO

Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19). Research has indicated that patients with pneumonia and sepsis have low vitamin C status and elevated oxidative stress. Administration of vitamin C to patients with pneumonia can decrease the severity and duration of the disease. Critically ill patients with sepsis require intravenous administration of gram amounts of the vitamin to normalize plasma levels, an intervention that some studies suggest reduces mortality. The vitamin has pleiotropic physiological functions, many of which are relevant to COVID-19. These include its antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions. Preliminary observational studies indicate low vitamin C status in critically ill patients with COVID-19. There are currently a number of randomized controlled trials (RCTs) registered globally that are assessing intravenous vitamin C monotherapy in patients with COVID-19. Since hypovitaminosis C and deficiency are common in low-middle-income settings, and many of the risk factors for vitamin C deficiency overlap with COVID-19 risk factors, it is possible that trials carried out in populations with chronic hypovitaminosis C may show greater efficacy. This is particularly relevant for the global research effort since COVID-19 is disproportionately affecting low-middle-income countries and low-income groups globally. One small trial from China has finished early and the findings are currently under peer review. There was significantly decreased mortality in the more severely ill patients who received vitamin C intervention. The upcoming findings from the larger RCTs currently underway will provide more definitive evidence. Optimization of the intervention protocols in future trials, e.g., earlier and sustained administration, is warranted to potentially improve its efficacy. Due to the excellent safety profile, low cost, and potential for rapid upscaling of production, administration of vitamin C to patients with hypovitaminosis C and severe respiratory infections, e.g., COVID-19, appears warranted.


Assuntos
Ácido Ascórbico/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Vitaminas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Deficiência de Ácido Ascórbico/complicações , Deficiência de Ácido Ascórbico/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Estado Terminal , Humanos , Estado Nutricional , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Vitaminas/farmacologia
11.
ESC Heart Fail ; 7(5): 3119-3123, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33121220

RESUMO

The present Perspective examined the latest evidence on the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and the incidence/mortality of coronavirus disease 2019 (COVID-19). Our critical appraisal from existing literature does not support discontinuation of ACEIs/ARBs in clinical practice as there is absence of solid evidence. However, we do recommend future research perspective in formulation and implementation of practice-changing guidelines.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Pandemias/estatística & dados numéricos , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/mortalidade , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Causas de Morte , Infecções por Coronavirus/mortalidade , Feminino , Mortalidade Hospitalar/tendências , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Análise de Sobrevida
12.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026746

RESUMO

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Erupção por Droga/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Antivirais/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/epidemiologia , Erupção por Droga/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pandemias , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia
13.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(8. Vyp. 2): 58-64, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33016678

RESUMO

The pandemic caused by the SARS-CoV-2 virus (COVID-19) made it necessary to evaluate in more detail the processes of neuroinflammation as an integral component of the pathogenesis of viral infection. The acute neuroinflammatory response includes the activation of resident tissue macrophages in the CNS and the subsequent release of various cytokines and chemokines, which probably activates oxidative stress, causing long-term neuronal damage. This makes urgent the search for drugs with indirect anti-inflammatory effects with proven effectiveness. From this point of view, it is worth further studying the treatment of patients with COVID-19 with dipyridamole, which, with its antiviral activity and anti-inflammatory effect, inhibiting acute inflammation and progressive fibrosis, is the drug of choice, especially for patients with early signs of elevated D-dimer concentrations and pronounced clinical symptoms of microangiopathy.


Assuntos
Infecções por Coronavirus , Inflamação , Doenças do Sistema Nervoso , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Betacoronavirus , Citocinas , Humanos , Doenças do Sistema Nervoso/virologia
14.
Front Immunol ; 11: 584514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101314

RESUMO

Physical trauma can be considered an unrecognized "pandemic" because it can occur anywhere and affect anyone and represents a global burden. Following severe tissue trauma, patients frequently develop acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) despite modern surgical and intensive care concepts. The underlying complex pathophysiology of life-threatening ALI/ARDS has been intensively studied in experimental and clinical settings. However, currently, the coronavirus family has become the focus of ALI/ARDS research because it represents an emerging global public health threat. The clinical presentation of the infection is highly heterogeneous, varying from a lack of symptoms to multiple organ dysfunction and mortality. In a particular subset of patients, the primary infection progresses rapidly to ALI and ARDS. The pathophysiological mechanisms triggering and driving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ALI/ARDS are still poorly understood. Although it is also generally unknown whether insights from trauma-induced ARDS may be readily translated to SARS-CoV-2-associated ARDS, it was still recommended to treat coronavirus-positive patients with ALI/ARDS with standard protocols for ALI/ARDS. However, this strategy was questioned by clinical scientists, because it was documented that some severely hypoxic SARS-CoV-2-infected patients exhibited a normal respiratory system compliance, a phenomenon rarely observed in ARDS patients with another underlying etiology. Therefore, coronavirus-induced ARDS was defined as a specific ARDS phenotype, which accordingly requires an adjusted therapeutic approach. These suggestions reflect previous attempts of classifying ARDS into different phenotypes that might overall facilitate ARDS diagnosis and treatment. Based on the clinical data from ARDS patients, two major phenotypes have been proposed: hyper- and hypo-inflammatory. Here, we provide a comparative review of the pathophysiological pathway of trauma-/hemorrhagic shock-induced ARDS and coronavirus-induced ARDS, with an emphasis on the crucial key points in the pathogenesis of both these ARDS forms. Therefore, the manifold available data on trauma-/hemorrhagic shock-induced ARDS may help to better understand coronavirus-induced ARDS.


Assuntos
Lesão Pulmonar Aguda/patologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Trombose/patologia , Lesão Pulmonar Aguda/virologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Citocinas/sangue , Humanos , Imunidade Inata/imunologia , Inflamação/patologia , Inflamação/virologia , Pulmão/patologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Trombose/virologia
18.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. Impr.) ; 46(7): 497-502, oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192622

RESUMO

ANTECEDENTES Y OBJETIVOS: La pandemia por COVID-19 ha puesto de manifiesto que las enfermedades cardiovasculares conllevan mayor riesgo de mortalidad. Han surgido dudas en cuanto a la terapia lipídica en estos pacientes. Nuestro objetivo en esta revisión es analizar la eficacia y la seguridad de la terapia hipolipemiante en los pacientes con COVID-19. MATERIAL Y MÉTODOS: Se realizó una revisión de la literatura científica en PubMed, informes CDC, NIH y NCBI SARS-CoV-2 utilizando las palabras clave: COVID-19, statins, ezetimibe, PCSK9 inhibitors, hypercholesterolemia and hypolipidemic drugs. RESULTADOS: Las estatinas se deben seguir utilizando en los pacientes con COVID-19 en base a su eficacia, seguridad, efectos inmunosupresores, antiinflamatorios, disponibilidad y accesibilidad. En función de los niveles de riesgo cardiovascular de estos pacientes puede ser necesario el empleo de estatinas de alta potencia y/o ezetimiba y/o inhibidores de la proproteína convertasa subtilisina (iPCSK9) en pacientes de alto y muy alto riesgo cardiovascular. Los pacientes tratados con iPCSK9 deben seguir con el tratamiento por sus efectos beneficiosos sobre la prevención de la enfermedad cardiovascular. Los pacientes con hipercolesterolemia familiar y COVID-19 son especialmente vulnerables a la enfermedad cardiovascular precoz y deben seguir recibiendo el tratamiento hipolipemiante intensivo. CONCLUSIONES: En los pacientes con COVID-19 la mayoría de las enfermedades cardiovasculares basales son de origen aterosclerótico, con peor pronóstico para los pacientes con alto riesgo y muy alto riesgo de enfermedad cardiovascular. En estos pacientes el tratamiento intensivo con estatinas y/o combinación fija con ezetimiba y/o iPCSK9 juega un papel fundamental


BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has shown that cardiovascular diseases carry a higher risk of mortality. Doubts have been raised regarding lipid therapy in these patients. The objectives are to analyze the efficacy and safety of lipid lowering therapy in patients with COVID-19. MATERIAL AND METHODS: A review of the scientific literature was conducted in PubMed, CDC Reports, NIH, and NCBI SARS-CoV-2 using the keywords: COVID-2, statins, ezetimibe, PCSK9 inhibitors, hypercholesterolemia, and hypolipidemic drugs. RESULTS: The statins should continue to use patients with COVID-19 based on their efficacy, safety, immunosuppressive effects, anti-inflammatory availability and accessibility. Depending on the cardiovascular risk levels of these patients, the use of high potency statins and/or ezetimibe and/or iPCSK9 may be necessary in patients with high and very high cardiovascular risk. Patients treated with iPCSK9 should continue treatment for its beneficial effects in preventing cardiovascular disease. Patients with familial hypercholesterolemia and COVID-19 are especially vulnerable to cardiovascular disease and should continue to receive severe lipid lowering therapy. CONCLUSIONS: In patients with COVID-19, the majority of baseline CVDs are of atherosclerotic origin, with the worst prediction for patients with high risk and very high risk of CVD. In these patients, intensive treatment with statins and/or fixed combination with ezetimibe and/or iPCSK9 plays a fundamental role


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vírus da SARS/patogenicidade , Hipolipemiantes/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Pandemias , Atenção Primária à Saúde/organização & administração , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Ezetimiba/administração & dosagem
19.
Trends Immunol ; 41(10): 856-859, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32863134

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mainly affects the lungs. Sarcoidosis is an autoinflammatory disease characterized by the diffusion of granulomas in the lungs and other organs. Here, we discuss how the two diseases might involve some common mechanistic cellular pathways around the regulation of autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Edema Pulmonar/tratamento farmacológico , Sarcoidose/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Autofagia/genética , Azitromicina/uso terapêutico , Betacoronavirus/crescimento & desenvolvimento , Cloroquina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Isoniazida/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/virologia , Edema Pulmonar/epidemiologia , Edema Pulmonar/genética , Edema Pulmonar/virologia , Rifampina/uso terapêutico , Sarcoidose/epidemiologia , Sarcoidose/genética , Sarcoidose/virologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença
20.
Molecules ; 25(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867349

RESUMO

Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CLpro) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CLpro based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CLpro inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2.


Assuntos
Antivirais/química , Betacoronavirus/química , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Inibidores de Proteases/química , Vírus da SARS/patogenicidade , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/classificação , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Domínio Catalítico , Infecções por Coronavirus/tratamento farmacológico , Cristalografia por Raios X , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Humanos , Cinética , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/classificação , Inibidores de Proteases/uso terapêutico , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Vírus da SARS/genética , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Especificidade por Substrato , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
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