RESUMEN
SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.
Asunto(s)
Antivirales/química , Metales/química , Metisazona/química , Simulación del Acoplamiento Molecular , SARS-CoV-2/química , Antivirales/metabolismo , Calcio/química , Calcio/metabolismo , Proteasas 3C de Coronavirus/química , Proteasas 3C de Coronavirus/metabolismo , Proteasas Similares a la Papaína de Coronavirus/química , Proteasas Similares a la Papaína de Coronavirus/metabolismo , ARN Polimerasa Dependiente de ARN de Coronavirus/química , ARN Polimerasa Dependiente de ARN de Coronavirus/metabolismo , Diseño de Fármacos , Humanos , Hierro/química , Hierro/metabolismo , Magnesio/química , Magnesio/metabolismo , Manganeso/química , Manganeso/metabolismo , Metales/metabolismo , Metisazona/metabolismo , Modelos Moleculares , Simulación de Dinámica Molecular , Unión Proteica , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Zinc/química , Zinc/metabolismo , Tratamiento Farmacológico de COVID-19RESUMEN
Background: The world urgently requires surrogate markers to diagnose COVID-19 and predict its progression. The severity is not easily predicted via currently used biomarkers. Critical COVID-19 patients need to be screened for hyperinflammation to improve mortality but expensive cytokine measurement is not routinely conducted in most laboratories. The neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker in patients with various diseases. We evaluated the diagnostic and prognostic accuracy of the NLR in COVID-19 patients.Methods: We searched for relevant articles in seven databases. The quantitative analysis was conducted if at least two studies were evaluating the NLR role in COVID-19.Results: We included 8,120 individuals, including 7,482 COVID-19 patients, from 32 articles. Patients with COVID-19 had significantly higher levels of NLR compared to negative individuals. Advanced COVID-19 stages had significantly higher levels of NLR than earlier stages.Expert Opinion: We found significantly higher levels of NLR in advanced stages compared to earlier stages of COVID-19 with good accuracy to diagnose and predict the disease outcome, especially mortality prediction. A close evaluation of critical SARS-CoV-2 patients and efficient early management are essential measures to decrease mortality. NLR could help in assessing the resource allocation in severe COVID-19 patients even in restricted settings.
Asunto(s)
COVID-19/sangre , COVID-19/mortalidad , Recuento de Linfocitos , Neutrófilos , Adulto , Anciano , COVID-19/etiología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement. The objectives are to: (1) provide an overview of the disruptions and challenges to neuroscience research caused by the COVID-19 pandemic, and; (2) put forth a set of consensus recommendations for strengthening research sustainability during and beyond the current pandemic. Specific recommendations are highlighted for adapting laboratory and human subject study activities to optimize safety. Complementary research activities are also outlined for both laboratory and clinical researchers if specific investigations are impossible because of regulatory or societal changes. The role of virtual platforms is discussed with respect to fostering new collaborations, scheduling research meetings, and holding conferences such that scientific collaboration and exchange of ideas can continue. Our hope is for these recommendations to serve as a valuable resource for investigators in the neurosciences and other research disciplines for current and future research disruptions.