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1.
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
2.
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
3.
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
4.
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
5.
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
6.
Reumatol. clín. (Barc.) ; 16(6): 437-446, nov.-dic. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194661

RESUMO

OBJETIVO: Generar las recomendaciones para la atención de pacientes con enfermedades reumáticas que reciben terapias inmunomoduladoras e inmunosupresoras (fármacos convencionales, biológicos y moléculas pequeñas) durante la pandemia por COVID-19. MATERIALES Y MÉTODOS: Las recomendaciones se realizaron utilizando el método Delphi como herramienta de acuerdo. Se conformó un panel de expertos con trayectoria académica y experiencia en investigación en reumatología. Se realizó la búsqueda de la literatura y se generó el cuestionario del ejercicio Delphi conformado por 42 preguntas. El grado de acuerdo se logró con el 80% de aprobación de los participantes. RESULTADOS: Se conformó un grupo de 11 reumatólogos de 7 ciudades del país. La tasa de respuesta fue del 100% para las 3 rondas de consulta. En la primera ronda se logró acuerdo en 35 preguntas, en la segunda ronda 37 y en la tercera ronda se logró el acuerdo de las 42 preguntas. CONCLUSIÓN: La recomendación para la mayoría de los tratamientos inmunomoduladores utilizados en reumatología es continuar con las terapias en pacientes que no tengan la infección y suspenderlas en aquellos con diagnóstico de SARS-CoV-2/COVID-19


OBJECTIVE: To produce recommendations for patients with rheumatological diseases receiving immunomodulatory and immunosuppressive therapies (conventional drugs, biologicals, and small molecules) during the COVID-19 pandemic. MATERIALS AND METHODS: The recommendations were determined using the Delphi method as an agreement tool. A panel of experts was formed, with academic backgrounds and research experience in rheumatology. A literature search was conducted and 42 questions were generated. The level of agreement was made with 80% of approval by the participants. RESULTS: A group of eleven rheumatologists from 7 cities in the country participated. The response rate was 100% for the three consultation rounds. In the first round, agreement was reached on 35 questions, on 37 in the second round, and on 42 questions in the third round. CONCLUSION: The recommendation for the majority of the pharmacological treatments used in rheumatology is to continue with immunomodulatory or immunosuppressive therapies in patients who do not have the infection, and to suspend it in patients with a diagnosis of SARS-CoV-2/COVID-19


Assuntos
Humanos , Doenças Reumáticas/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Antirreumáticos/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Doenças Reumáticas/complicações , Padrões de Prática Médica , Suspensão de Tratamento/tendências , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos
7.
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
8.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(11): 970-974, 2020 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-33137863

RESUMO

The novel coronavirus pneumonia (COVID-19) is still in a serious situation. There is no specific therapeutic drug for COVID-19. At present, drugs, including lopinavir/ritonavir, chloroquine phosphate, abidol, IFN-α atomization and ribavirin, are commonly used in clinical practice. However, further clinical trials are needed to evaluate the efficacy and safety of these drugs. Other potential drugs that may be effective for COVID-19, are worthy of attention, including IL-6 monoclonal antibody, tyrosine protein kinase 1/2 inhibitor, cell therapy drugs, etc. This paper reviews these potential therapeutic drugs for COVID-19.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Combinação de Medicamentos , Humanos , Pandemias
9.
Medicina (Kaunas) ; 56(11)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33137936

RESUMO

Coronavirus disease (COVID-19) started in Wuhan (China) at the end of 2019, and then increased rapidly. In patients with severe acute respiratory distress syndrome (ARDS) caused by COVID-19, venovenous extracorporeal membrane oxygenation (VV-ECMO) is considered a rescue therapy that provides adequate gas exchange. The way in which mechanical ventilation is applied during VV-ECMO is not clear, however it is associated with prognosis. Currently, the mortality rate of COVID-19 patients that receive VV-ECMO stands at approximately 50%. Here, we report three patients that successfully recovered from COVID-19-induced ARDS after VV-ECMO and implementation of an ultra-protective ventilation. This ventilation strategy involved maintaining a peak inspiratory pressure of ≤20 cmH2O and a positive end-expiratory pressure (PEEP) of ≤ 10 cmH2O, which are lower values than have been previously reported. Thus, we suggest that this ultra-protective ventilation be considered during VV-ECMO as it minimizes the ventilator-induced lung injury.


Assuntos
Infecções por Coronavirus/terapia , Oxigenação por Membrana Extracorpórea/métodos , Glucocorticoides/uso terapêutico , Pneumonia Viral/terapia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Adulto/terapia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade , Pandemias
10.
Medicina (Kaunas) ; 56(11)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138045

RESUMO

BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.


Assuntos
Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Coinfecção/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Mortalidade Hospitalar , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Antígenos de Bactérias/urina , Azitromicina/uso terapêutico , Betacoronavirus , Ceftriaxona/uso terapêutico , Cobicistat/uso terapêutico , Coinfecção/urina , Infecções por Coronavirus/complicações , Estudos Transversais , Darunavir/uso terapêutico , Combinação de Medicamentos , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Levofloxacino/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Pandemias , Pneumonia Pneumocócica/complicações , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/urina , Pneumonia Viral/complicações , Estudos Retrospectivos , Ritonavir/uso terapêutico , Streptococcus pneumoniae/imunologia
12.
Medwave ; 20(9): e8049, 2020 Oct 27.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-33141814

RESUMO

In December 2019, a new species of pneumonia-causing betacoronavirus was identified in Wuhan, China, which was later identified as SARS-CoV-2. This RNA virus presents certain similarities with other viruses of the same genetic material. It has been seen that infection by human immunodeficiency virus resembles the infection by SARS-CoV-2 in various aspects. In this comment, we present some of the virological, immunological, clinical, and pharmacological similarities between HIV and SARS-CoV-2, which could allow us to understand the immunopathogenesis of COVID-19 better, as well as make some decisions in regarding antiviral management.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Infecções por HIV/virologia , HIV/isolamento & purificação , Pneumonia Viral/virologia , Antivirais/farmacologia , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , HIV/imunologia , Infecções por HIV/imunologia , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia
13.
Trials ; 21(1): 904, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129363

RESUMO

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pirazinas/uso terapêutico , Amidas/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Feminino , Interações Hospedeiro-Patógeno , Humanos , Hidroxicloroquina/efeitos adversos , Pacientes Internados , Masculino , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento
14.
Kardiologiia ; 60(9): 4-21, 2020 Oct 05.
Artigo em Russo | MEDLINE | ID: mdl-33131470

RESUMO

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.


Assuntos
Colchicina , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticoagulantes/uso terapêutico , Betacoronavirus , Colchicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Estudos Prospectivos , Pirazóis
18.
Front Immunol ; 11: 569611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133083

RESUMO

COVID-19 caused by SARS CoV2 emerged in China at the end of 2019 and soon become a pandemic. Since the virus is novel, pre-existing CoV2-specific immunity is not expected to exist in humans, although studies have shown presence of CoV2 cross-reactive T cells in unexposed individuals. Lack of effective immunity in most individuals along with high infectiousness of the virus has resulted in massive global public health emergency. Intense efforts are on to study viral pathogenesis and immune response to help guide prophylactic and therapeutic interventions as well as epidemiological assessments like transmission modeling. To develop an effective vaccine or biologic therapeutic, it is critical to understand the immune correlates of COVID-19 control. At the same time, whether immunity in recovered individuals is effective for preventing re-infection will be important for informing interventions like social distancing. Key questions that are being investigated regarding immune response in COVID-19 which will help these efforts include, investigations of immune response that distinguishes patients with severe versus mild infection or those that recover relative to those that succumb, durability of immunity in recovered patients and relevance of developed immunity in a cured patient for protection against re-infection as well as value of convalescent plasma from recovered patients as a potential therapeutic modality. This is a broad and rapidly evolving area and multiple reports on status of innate and adaptive immunity against SARS-CoV2 are emerging on a daily basis. While many questions remain unanswered for now, the purpose of this focused review is to summarize the current understanding regarding immune correlates of COVID-19 severity and resolution in order to assist researchers in the field to pursue new directions in prevention and control.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Infecções por Coronavirus/tratamento farmacológico , Citocinas/imunologia , Humanos , Mediadores da Inflamação/imunologia , Gravidade do Paciente , Recidiva , Linfócitos T/imunologia , Vacinas Virais/imunologia
19.
Front Immunol ; 11: 574508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133090

RESUMO

COVID-19 is a global pandemic currently in an acute phase of rapid expansion. While public health measures remain the most effective protection strategy at this stage, when the peak passes, it will leave in its wake important health problems. Historically, very few viruses have ever been eradicated. Instead, the virus may persist in communities causing recurrent local outbreaks of the acute infection as well as several chronic diseases that may arise from the presence of a "suppressed" virus or as a consequence of the initial exposure. An ideal solution would be an anti-viral medication that (i) targets multiple stages of the viral lifecycle, (ii) is insensitive to frequent changes of viral phenotype due to mutagenesis, (iii) has broad spectrum, (iv) is safe and (v) also targets co-morbidities of the infection. In this Perspective we discuss a therapeutic approach that owns these attributes, namely "lipid raft therapy." Lipid raft therapy is an approach aimed at reducing the abundance and structural modifications of host lipid rafts or at targeted delivery of therapeutics to the rafts. Lipid rafts are the sites of the initial binding, activation, internalization and cell-to-cell transmission of SARS-CoV-2. They also are key regulators of immune and inflammatory responses, dysregulation of which is characteristic to COVID-19 infection. Lipid raft therapy was successful in targeting many viral infections and inflammatory disorders, and can potentially be highly effective for treatment of COVID-19.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Microdomínios da Membrana/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Animais , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Sistemas de Liberação de Medicamentos , Humanos , Microdomínios da Membrana/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia
20.
PLoS One ; 15(11): e0241947, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166346

RESUMO

BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We propose the protocol described below to perform an individual-patient data (IPD) network meta-analysis (NMA) in order to evaluate the efficacies of different antiviral drugs to treat patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: We will search the Medline, EMBASE, Cochrane Library, SinoMed, CNKI and VIP databases from their inceptions through July 2020. There will be no restrictions on language, publication year, or publication type. Randomized clinical trials (RCTs) and prospective cohort studies with antiviral treatments for COVID-19 will be considered. Two reviewers will independently select studies and collect data. Risk-of-bias assessments will be completed using the Cochrane risk-of-bias scale. Primary outcome will be the COVID-19 recovery rate. We will combine aggregated data from IPD with the NMA in a single model, compare the effects of different antiviral drugs on patient-relevant efficacy, and rank the results to decide which is the most effective. TRIAL REGISTRATION: PROSPERO registration number: CRD42020167038.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Bases de Dados Factuais , Humanos , Metanálise em Rede , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Resultado do Tratamento
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