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1.
Med. clín (Ed. impr.) ; 156(1): 7-12, ene. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-ET2-7753

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
2.
Medicine (Baltimore) ; 100(1): e23582, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429732

RESUMO

ABSTRACT: COVID-19 is causing a high influx of patients suffering from serious respiratory complications leading the necessity to find effective therapies. These patients seem to present with cytokine perturbation and high levels of IL6. Tocilizumab and sarilumab could be effective in this condition.We retrospectively collected data about 112 consecutive hospitalized in a single center.Fifty (IL6 group) treated with tocilizumab (8 mg/kg intravenously [IV], 2 infusions 12 hours apart) or sarilumab 400 mg IV once and 62 treated with the standard of care but not anti-cytokine drugs (CONTROL group).To determine whether anti-IL6 drugs are effective in improving prognosis and reducing hospitalization times and mortality in COVID-19 pneumonia.To date 84% (42/50) of IL6 group patients have already been discharged and only 2/50 are still recovered and intubated in intensive care. Six/fifty patients (12%) died: 5/6 due to severe respiratory failure within a framework of severe acute respiratory distress syndrome (ARDS), 1 suffered an acute myocardial infarction, and 1 died of massive pulmonary thromboembolism. There were no adverse treatment events or infectious complications. Compared to the CONTROL group they showed a lower mortality rate (12% versus 43%), for the same number of complications and days of hospitalization.Anti-IL6 drugs seem to be effective in the treatment of medium to severe forms of COVID-19 pneumonia reducing the risk of mortality due to multi-organ failure, acting at the systemic level and reducing inflammation levels and therefore microvascular complications. However, it is essential to identify the best time for treatment, which, if delayed, is rendered useless as well as counterproductive. Further studies and ongoing clinical trials will help us to better define patients eligible as candidates for more aggressive intervention.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos
3.
N Engl J Med ; 384(1): 20-30, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33332779

RESUMO

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , /tratamento farmacológico , Adulto , Idoso , /mortalidade , Progressão da Doença , Feminino , Hospitalização , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Taxa de Sobrevida
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118825, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32866803

RESUMO

Novel antiviral active molecule 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl)acetamide has been synthesised and characterized by FT-IR and FT-Raman spectra. The equilibrium geometry, natural bond orbital calculations and vibrational assignments have been carried out using density functional B3LYP method with the 6-311G++(d,p) basis set. The complete vibrational assignments for all the vibrational modes have been supported by normal coordinate analysis, force constants and potential energy distributions. A detailed analysis of the intermolecular interactions has been performed based on the Hirshfeld surfaces. Drug likeness has been carried out based on Lipinski's rule and the absorption, distribution, metabolism, excretion and toxicity of the title molecule has been calculated. Antiviral potency of 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro-phenyl) acetamide has been investigated by docking against SARS-CoV-2 protein. The optimized geometry shows near-planarity between the phenyl ring and the pyrimidine ring. Differences in the geometries due to the substitution of the most electronegative fluorine atom and intermolecular contacts due to amino pyrimidine were analyzed. NBO analysis reveals the formation of two strong stable hydrogen bonded N-H···N intermolecular interactions and weak intramolecular interactions C-H···O and N-H···O. The Hirshfeld surfaces and consequently the 2D-fingerprint confirm the nature of intermolecular interactions and their quantitative contributions towards the crystal packing. The red shift in N-H stretching frequency exposed from IR substantiate the formation of N-H···N intermolecular hydrogen bond. Drug likeness and absorption, distribution, metabolism, excretion and toxicity properties analysis gives an idea about the pharmacokinetic properties of the title molecule. The binding energy -8.7 kcal/mol of the nonbonding interaction present a clear view that 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl) acetamide can irreversibly interact with SARS-CoV-2 protease.


Assuntos
Antivirais/química , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/farmacocinética , Betacoronavirus/enzimologia , Cristalografia por Raios X , Cisteína Endopeptidases , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Dinâmica não Linear , Inibidores de Proteases/farmacocinética , Conformação Proteica , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Termodinâmica , Vibração
5.
J Infect Chemother ; 27(1): 94-98, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32988730

RESUMO

The effect of systemic corticosteroids on clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains controversial. While the use of corticosteroids raises concerns regarding delayed viral clearance, secondary infections, and long-term complications that can lead to increased mortality, corticosteroids have the potential to reduce mortality if used appropriately. Herein, we report good outcomes in two patients with COVID-19 who received systemic corticosteroids as adjunctive therapy. An 83-year-old man with hypertension and smoking history and a 62-year-old man with a drinking habit were transferred to our hospital with a diagnosis of COVID-19. The patients developed general malaise and loss of appetite with persistent high fever. Despite the prescription of antiviral drugs, their hypoxemia progressed rapidly. However, after the introduction of systemic corticosteroids, their symptoms improved as the fever decreased, and their hypoxemia gradually improved. These results suggest that some patients with COVID-19 may benefit from the appropriate use of systemic corticosteroids as adjunctive therapy.


Assuntos
Corticosteroides/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Metilprednisolona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Antivirais/uso terapêutico , Betacoronavirus , Terapia Combinada , Infecções por Coronavirus/epidemiologia , Humanos , Hipertensão/epidemiologia , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Fumar/epidemiologia , Neoplasias Gástricas/epidemiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Environ Res ; 192: 110294, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33022215

RESUMO

The rapid spread of COVID-19 has led to nationwide lockdowns in many countries. The COVID-19 pandemic has played serious havoc on economic activities throughout the world. Researchers are immensely curious about how to give the best protection to people before a vaccine becomes available. The coronavirus spreads principally through saliva droplets. Thus, it would be a great opportunity if the virus spread could be controlled at an early stage. The face mask can limit virus spread from both inside and outside the mask. This is the first study that has endeavoured to explore the design and fabrication of an antiviral face mask using licorice root extract, which has antimicrobial properties due to glycyrrhetinic acid (GA) and glycyrrhizin (GL). An electrospinning process was utilized to fabricate nanofibrous membrane and virus deactivation mechanisms discussed. The nanofiber mask material was characterized by SEM and airflow rate testing. SEM results indicated that the nanofibers from electrospinning are about 15-30 µm in diameter with random porosity and orientation which have the potential to capture and kill the virus. Theoretical estimation signifies that an 85 L/min rate of airflow through the face mask is possible which ensures good breathability over an extensive range of pressure drops and pore sizes. Finally, it can be concluded that licorice root membrane may be used to produce a biobased face mask to control COVID-19 spread.


Assuntos
Antivirais , Betacoronavirus , Coronavirus , Pneumonia Viral , Antivirais/uso terapêutico , Glycyrrhiza , Humanos , Máscaras , Nanofibras , Pandemias , Pneumonia Viral/tratamento farmacológico
7.
J Ethnopharmacol ; 265: 113319, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32882361

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the outbreaks such as SARS, bird flu and swine flu, which we frequently encounter in our century, we need fast solutions with no side effects today more than ever. Due to having vast ethnomedical experience and the richest flora (34% endemic) of Europe and the Middle East, Turkey has a high potential for research on this topic. Plants that locals have been using for centuries for the prevention and treatment of influenza can offer effective alternatives to combat this problem. In this context, 224 herbal taxa belonging to 45 families were identified among the selected 81 studies conducted in the seven regions of Turkey. However, only 35 (15.6%) of them were found to be subjected to worldwide in vitro and in vivo research conducted on anti-influenza activity. Quercetin and chlorogenic acid, the effectiveness of which has been proven many times in this context, have been recorded as the most common (7.1%) active ingredients among the other 56 active substances identified. AIM OF THE STUDY: This study has been carried out to reveal the inventory of plant species that have been used in flu treatment for centuries in Turkish folk medicine, which could be used in the treatment of flu or flu-like pandemics, such as COVID 19, that humanity has been suffering with, and also compare them with experimental studies in the literature. MATERIALS AND METHODS: The investigation was conducted in two stages on the subject above by using electronic databases, such as Web of Science, Scopus, ScienceDirect, ProQuest, Medline, Cochrane Library, EBSCO, HighWire Press, PubMed and Google Scholar. The results of both scans are presented in separate tables, together with their regional comparative analysis. RESULTS: Data obtained on taxa are presented in a table, including anti-influenza mechanism of actions and the active substances. Rosa canina (58.7%) and Mentha x piperita (22.2%) were identified as the most common plants used in Turkey. Also, Sambucus nigra (11.6%), Olea europaea (9.3%), Eucalyptus spp., Melissa officinalis, and Origanum vulgare (7.0%) emerged as the most investigated taxa. CONCLUSION: This is the first nationwide ethnomedical screening work conducted on flu treatment with plants in Turkey. Thirty-nine plants have been confirmed in the recent experimental anti-influenza research, which strongly shows that these plants are a rich pharmacological source. Also, with 189 (84.4%) taxa, detections that have not been investigated yet, they are an essential resource for both national and international pharmacological researchers in terms of new natural medicine searches. Considering that the production of antimalarial drugs and their successful use against COVID-19 has begun, this correlation was actually a positive and remarkable piece of data, since there are 15 plants, including Centaurea drabifolia subsp. Phlocosa (an endemic taxon), that were found to be used in the treatment of both flu and malaria.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus , Etnofarmacologia/métodos , Influenza Humana/tratamento farmacológico , Pandemias , Plantas Medicinais/classificação , Pneumonia Viral , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Medicina Tradicional/métodos , Fitoterapia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Turquia
8.
Acta Pharm ; 71(2): 175-184, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151168

RESUMO

Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Dipeptidil Peptidase 4/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Fosfato de Sitagliptina/farmacologia , Fosfato de Sitagliptina/uso terapêutico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Biologia Computacional , Infecções por Coronavirus/complicações , Cristalografia por Raios X , Mineração de Dados , Complicações do Diabetes/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Reposicionamento de Medicamentos , Redes Reguladoras de Genes , Humanos , Estrutura Molecular , Pandemias , Pneumonia Viral/complicações
9.
J Infect Chemother ; 27(1): 99-102, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33023821

RESUMO

We present three patients affected by pulmonary squamous cell carcinoma, metastatic esophageal cancer and advanced non-Hodgkin lymphoma, who incurred in coronavirus 2019 (COVID-19) infection during the early phase of epidemic wave in Italy. All patients presented with fever. Social contact with subject positive for COVID-19 was declared in only one of the three cases. In all cases, laboratory findings showed lymphopenia and elevated C-reactive protein (CRP). Chest x-ray and computed tomography showed bilateral ground-glass opacities, shadowing, interstitial abnormalities, and "crazy paving" pattern which evolved with superimposition of consolidations in one patient. All patients received antiviral therapy based on ritonavir and lopinavir, associated with hydroxychloroquine. Despite treatment, two patients with advanced cancers died after 39 and 17 days of hospitalization, while the patient with lung cancer was dismissed at home, in good conditions.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Neoplasias/complicações , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Surtos de Doenças , Quimioterapia Combinada , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/tratamento farmacológico , Evolução Fatal , Humanos , Itália , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Ann Med ; 53(1): 117-134, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33095083

RESUMO

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and anti-inflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.


Assuntos
Antimaláricos/uso terapêutico , Cardiotoxicidade/etiologia , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antimaláricos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Hidroxicloroquina/farmacologia , Pandemias
11.
Acta Pharm ; 71(2): 163-174, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151166

RESUMO

The current outbreak of novel coronavirus (COVID-19) infections urges the need to identify potential therapeutic agents. Therefore, the repurposing of FDA-approved drugs against today's diseases involves the use of de-risked compounds with potentially lower costs and shorter development timelines. In this study, the recently resolved X-ray crystallographic structure of COVID-19 main protease (Mpro) was used to generate a pharmacophore model and to conduct a docking study to capture antiviral drugs as new promising COVID-19 main protease inhibitors. The developed pharmacophore successfully captured five FDA-approved antiviral drugs (lopinavir, remdesivir, ritonavir, saquinavir and raltegravir). The five drugs were successfully docked into the binding site of COVID-19 Mpro and showed several specific binding interactions that were comparable to those tying the co-crystallized inhibitor X77 inside the binding site of COVID-19 Mpro. Three of the captured drugs namely, remdesivir, lopinavir and ritonavir, were reported to have promising results in COVID-19 treatment and therefore increases the confidence in our results. Our findings suggest an additional possible mechanism of action for remdesivir as an antiviral drug inhibiting COVID-19 Mpro. Additionally, a combination of structure-based pharmacophore modeling with a docking study is expected to facilitate the discovery of novel COVID-19 Mpro inhibitors.


Assuntos
Infecções por Coronavirus/enzimologia , Pneumonia Viral/enzimologia , Inibidores de Proteases/farmacologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/química , Alanina/farmacologia , Alanina/uso terapêutico , Antivirais/química , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Cristalografia por Raios X , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos , Humanos , Modelos Químicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Pandemias , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteases/química , Relação Estrutura-Atividade
12.
J Intensive Care Med ; 36(2): 135-156, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33317385

RESUMO

In December 2019, COVID-19, a severe respiratory illness caused by the new coronavirus SARS-CoV-2 (COVID-19) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies' recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working," the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically. The review concludes with a comparison of published multi-national mortality data with MATH+ center outcomes.


Assuntos
/tratamento farmacológico , Protocolos Clínicos , Unidades de Terapia Intensiva/organização & administração , Pneumonia Viral/tratamento farmacológico , Ácido Ascórbico/uso terapêutico , Quimioterapia Combinada , Heparina/uso terapêutico , Hospitalização , Humanos , Metilprednisolona/uso terapêutico , Pneumonia Viral/epidemiologia , Respiração Artificial , Tiamina/uso terapêutico
13.
Rev. esp. cardiol. Supl. (Ed. impresa) ; 20(supl.E): 27-32, dic. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-195344

RESUMO

La pandemia ocasionada por la rápida expansión del SARS-CoV-2 ha producido la mayor crisis sanitaria de la época moderna. La estrecha relación del virus con la enzima de conversión de la angiotensina ha suscitado un torrente de especulaciones por el posible papel del sistema renina-angiotensina-aldosterona (SRAA) en la regulation de la infection. La alerta generada ha cuestionado el empleo de fármacos inhibidores del SRAA, tanto los inhibidores de la enzima de conversión de la angiotensina como los antagonistas del receptor de la angiotensina II. está situación ha motivado la publication de varios estudios que no han encontrado asociación entre el uso de inhibidores del SRAA y una mayor susceptibilidad a la infección o a una peor evolution clínica. En está revisión se abordan los aspectos más relevantes de la interacción del SARS-CoV-2 con el SRAA y las implicaciones clínicas en torno al uso de inhibidores del SRAA durante la pandemia


The pandemic caused by the rapid spread of the SARS-CoV-2 virus has produced the greatest health crisis of modern times. The close relationship between the virus and angiotensin-II converting enzyme has provoked a torrent of speculation about the possible role of the renin-angiotensin-aldosterone system (RAAS) in mediating infection. The subsequent alarm has raised questions about the use of RAAS inhibitors, such as angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers. The result has been the publication of several studies that have failed to find an association between the use of RAAS inhibitors and greater susceptibility to infección or a worse clínical outlook. This review considers the most significant aspects of the interaction between SARS-CoV-2 and the RAAS and the clínical implications of using RAAS inhibitors during the pandemic


Assuntos
Humanos , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Pandemias , Sistema Renina-Angiotensina/fisiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico
14.
Rev. esp. cardiol. Supl. (Ed. impresa) ; 20(supl.E): 33-39, dic. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-195345

RESUMO

La búsqueda de tratamientos eficaces contra la pandemia actual por COVID-19 ha supuesto un desafïo enorme para la comunidad científica. De hecho, no existe todavía un tratamiento claramente efectivo, además de las medidas de soporte, contra el SARS-CoV-2. Los esfuerzos se han centrado en recuperar fármacos antivirales empleados previamente contra otras infecciónes viricas y en el uso de antiinflamatorios, dado el estado hiperinflamatorio que pueden sufrir los pacientes con COVID-19 y que se asocia con un peor pronóstico de la enfermedad. Sin embargo, estos fármacos, usados en ocasiones de manera compasiva, pueden causar efectos secundarios graves o interacciones farmacológicas que se debe conocer. El objetivo de este artículo es revisar el estado actual del conocimiento sobre los tratamientos farmacológicos más usados contra la COVID-19 en nuestro medio, prestando una especial atención a los efectos secundarios y las interacciones farmacológicas relacionadas con el sistema cardiovascular


The search for effective treatments against COVID-19 in the current pandemic has presented the scientific community with an enormous challenge. In fact, there is still no effective treatment for SARS-CoV-2 infection, apart from supportive measures. Research has focused on re-examining antiviral drugs that were previously used against other viral infections and on the use of anti-inflammatories, since COVID-19 patients can develop a hyperinflammatory state, which is associated with a poorer disease prognosis. However, these drugs, sometimes administered on a compassionate-use basis, can cause serious side effects or drug interactions that we should be aware of. The aim of this article is to provide an overview of what is currently known about the pharmacological therapies most frequently used against COVID-19 in our field, while paying particular attention to the adverse events and drug interactions that can affect the cardiovascular system


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pandemias , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Sistema Cardiovascular/efeitos dos fármacos , Interações Medicamentosas
18.
Neurología (Barc., Ed. impr.) ; 35(9): 628-632, nov.-dic. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192758

RESUMO

INTRODUCCIÓN: En los últimos meses han surgido dudas por parte de pacientes, médicos de familia y neurólogos sobre la posibilidad de que algunos de los fármacos que habitualmente se utilizan en cefaleas y neuralgias puedan facilitar o complicar la infección por el SARS-CoV-2. MATERIAL Y MÉTODOS: Hemos recabado información sobre el posicionamiento de sociedades científicas, así como de las distintas Agencias de Medicamentos (americana, europea y española) para poder esclarecer dudas respecto al uso de fármacos como lisinopril, candesartán, ibuprofeno, corticoides, carbamazepina, anticuerpos monoclonales contra el péptido relacionado con el gen de la calcitonina (CGRP) durante la pandemia por COVID-19. RESULTADOS: Planteamos recomendaciones acerca del uso de fármacos habituales en el tratamiento de las cefaleas en el contexto de la pandemia por COVID-19, basándonos en las evidencias de las que disponemos en el momento actual. CONCLUSIONES: Actualmente no existe ningún argumento científico robusto para contraindicar formalmente ninguno de los tratamientos que se emplean en cefaleas y neuralgias


INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin generelated peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias


Assuntos
Humanos , Sociedades Médicas , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pandemias , Cefaleia/tratamento farmacológico , Cefaleia/virologia , Neuralgia/tratamento farmacológico , Neuralgia/virologia , Espanha , Interações Medicamentosas
20.
Ars pharm ; 61(4): 253-257, oct.-dic. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193586

RESUMO

INTRODUCCIÓN: La Enfermedad por coronavirus 2019 (COVID-19) causada por el virus SARS-CoV-2, con característica de infectar el tracto respiratorio causando un síndrome respiratorio agudo como paso inicial para ingresar a la célula huésped el virus usa los receptores ACE II y la proteína transmembrana TMPRSS2 para causar la infección, Por lo que se ha descrito diferentes tipos de fármacos para realizar su inhibición en la adhesión del paso inicial. METODOLOGÍA: Revisión no sistemática de artículos con la ayuda de palabras clave preestablecidas. RESULTADOS: En esta revisión presentaremos fármacos que inhiben este tipo de receptor, por lo tanto, estos medicamentos podrían considerarse candidatos potenciales para mitigar la propagación del SARS-CoV-2


INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus with characteristic of infecting the respiratory tract, causing severe acute respiratory syndrome. The virus uses the ACE II receptors and the transmembrane protein TMPRSS2 initial step to enter the host cell, this contribution described different types of drug, to perform its inhibition in initial step adhesion. METHODOLOGY: Non-systematic review of articles with the help of preset keywords. RESULTS: In this review we will present drugs that inhibitors of this type of receptor therefore these drugs could be considered potential candidates to mitigate the spread of SARS-CoV-2


Assuntos
Humanos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Serina Endopeptidases/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores de Serino Proteinase/farmacologia , Serina Endopeptidases/farmacologia
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