RESUMEN
Vitiligo is an acquired autoimmune skin disorder, clinically characterized by distinct white macules and patches resulting from progressive melanocyte destruction. JAK-STAT pathway plays an important role in the loss of epidermal melanocytes. Baricitinib can block the JAK-STAT pathway and the downstream chemokines as a new JAK1/2 inhibitor. In this report, we describe the successful treatment of 2 patients with oral baricitinib combined with NB-UVB phototherapy, which provides a good alternative and supplementary to treat refractory vitiligo.
RESUMEN
A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (Mpro), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 µmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC50 value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substrate-binding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.
Asunto(s)
Proteasas Similares a la Papaína de Coronavirus/química , Ensayos Analíticos de Alto Rendimiento/métodos , Inhibidores de Proteasas/química , Antivirales/química , Antivirales/metabolismo , Antivirales/uso terapéutico , Sitios de Unión , COVID-19/virología , Proteasas Similares a la Papaína de Coronavirus/genética , Proteasas Similares a la Papaína de Coronavirus/metabolismo , Cristalografía por Rayos X , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos , Humanos , Imidazoles/química , Imidazoles/metabolismo , Imidazoles/uso terapéutico , Concentración 50 Inhibidora , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Naftoquinonas/química , Naftoquinonas/metabolismo , Naftoquinonas/uso terapéutico , Inhibidores de Proteasas/metabolismo , Inhibidores de Proteasas/uso terapéutico , Estructura Terciaria de Proteína , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , SARS-CoV-2/aislamiento & purificación , Tratamiento Farmacológico de COVID-19RESUMEN
OBJECTIVE: Study on the antibacterial activity of Viola yedoensis and the antibacterial active compounds. METHOD: The chemical compositions were isolated by means of solvent extraction, column chromatography on silica gel, sephadex LH-20 and crystallization. The antibacterial activities were tested by Neo-Sensitab disk-diffusion method, nephelometric analysis and plating method. RESULT: One new compound (4) along with three known compounds were isolated from this plant for the first time and were identified as aesculetin (1), 6,7-dimethoxycoumarin (2), scopoletin (3) and 5-methoxy-7-hydroxymethylcoumarin (4), respectively. All the compounds showed antibacterial and antibactericidal activities at varying degree on Streptococcus Aureas, S. agalactiae, S. uberis, S. dysgalactiae, E. coli and Salmonella, of which 1 was most active with 0.031- 0.313 g x L(-1) of minimal inhibitory concentrations (MIC) and 0.313 - 0.625 g x L(-1) of minimal bactericidal concentrations (MBC). CONCLUSION: Viola yedoensis has a broad spectrum of antibacterial activity on animal pathogenic bacteria, and coumarins may be the main antibacterial activity ingredients.
Asunto(s)
Antibacterianos/farmacología , Extractos Vegetales/farmacología , Viola/química , Antibacterianos/análisis , Bacterias/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/análisisRESUMEN
OBJECTIVE: To study the protection of seed oil of Hippophae rhamnoides on ischemic cerebral infarction in rats and the mechanism of the action. METHOD: Focal cerebral ischemia model was made by middle cerebral artery occlusion(MCAO) in rats. Behavior obstacles of rats were observed. Cerebral infarction volume was determined by Megnetic Resonance Imaging(MRI). RESULT: Seed oil of Hippophae rhamnides 0.7 and 0.35 g.kg-1 could markedly reduce infarction volume after occlusion of middle cerebral artery in rats and also could ameliorate the behavior obstacles of rats. CONCLUSION: These results suggested that seed oil of Hippophae rhamnoides had distinct protection to ischemic cerebral infarction in rats.