A systems-level study reveals host-targeted repurposable drugs against SARS-CoV-2 infection.

Understanding the mechanism of SARS-CoV-2 infection and identifying potential therapeutics are global imperatives. Using a quantitative systems pharmacology approach, we identified a set of repurposable and investigational drugs as potential therapeutics against COVID-19. These were deduced from the gene expression signature of SARS-CoV-2-infected A549 cells screened against Connectivity Map and prioritized by network proximity analysis with respect to disease modules in the viral-host interactome. We also identified immuno-modulating compounds aiming at suppressing hyperinflammatory responses in severe COVID-19 patients, based on the transcriptome of ACE2-overexpressing A549 cells. Experiments with Vero-E6 cells infected by SARS-CoV-2, as well as independent syncytia formation assays for probing ACE2/SARS-CoV-2 spike protein-mediated cell fusion using HEK293T and Calu-3 cells, showed that several predicted compounds had inhibitory activities. Among them, salmeterol, rottlerin, and mTOR inhibitors exhibited antiviral activities in Vero-E6 cells; imipramine, linsitinib, hexylresorcinol, ezetimibe, and brompheniramine impaired viral entry. These novel findings provide new paths for broadening the repertoire of compounds pursued as therapeutics against COVID-19.

Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication.

SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clinical trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical for SARS-CoV-2 infection. A drug-protein interaction-based secondary screen confirmed compounds, such as the ATR kinase inhibitor berzosertib and torin2 with anti-SARS-CoV-2 activity. Berzosertib exhibited potent antiviral activity against SARS-CoV-2 in multiple cell types and blocked replication at the post-entry step. Berzosertib inhibited replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well. Our study highlights key promising kinase inhibitors to constrain coronavirus replication as a host-directed therapy in the treatment of COVID-19 and beyond as well as provides an important mechanism of host-pathogen interactions.

Electron Transfer Induced Decomposition in Potassium-Nitroimidazoles Collisions: An Experimental and Theoretical Work.

Electron transfer induced decomposition mechanism of nitroimidazole and a selection of analogue molecules in collisions with neutral potassium (K) atoms from 10 to 1000 eV have been thoroughly investigated. In this laboratory collision regime, the formation of negative ions was time-of-flight mass analyzed and the fragmentation patterns and branching ratios have been obtained. The most abundant anions have been assigned to the parent molecule and the nitrogen oxide anion (NO2-) and the electron transfer mechanisms are comprehensively discussed. This work focuses on the analysis of all fragment anions produced and it is complementary of our recent work on selective hydrogen loss from the transient negative ions produced in these collisions. Ab initio theoretical calculations were performed for 4-nitroimidazole (4NI), 2-nitroimidazole (2NI), 1-methyl-4- (Me4NI) and 1-methyl-5-nitroimidazole (Me5NI), and imidazole (IMI) in the presence of a potassium atom and provided a strong basis for the assignment of the lowest unoccupied molecular orbitals accessed in the collision process.

Impact of the Intensive Program of Emotional Intelligence (IPEI) on work supervisors / Impacto del Programa de Inteligencia Emocional Intensivo (PIEI) en supervisores de trabajo

Background: This study aimed to evaluate the effect of the Intensive Program of Emotional Intelligence (IPEI; Fernández, 2016; Férreo, 2016) on middle managers’ emotional intelligence, as this variable may have a significant impact on personal satisfaction, task performance, and the work environment. Method: The intervention was applied to work team supervisors in a large call center, as it is an overlooked sector in this topic. Two-hundred and eighty-two supervisors from a Madrid-based, Spanish multinational (51.4% men and 48.6% women) participated in this study. Participants were assigned to the experimental group (n = 190) or the control group (n = 92) by availability, according to management decision. All supervisors filled in two questionnaires to evaluate the different components of intrapersonal emotional intelligence (i.e., attention, clarity, and repair; TMMS-24; Fernández-Berrocal, Extremera, & Ramos, 2004) and cognitive and affective empathy (i.e., perspective taking, emotion understanding, empathic joy, and personal distress; TECA; López-Pérez, Fernández, & Abad, 2008). Results: The findings showed an increase in the studied variables for the experimental group. Conclusions: The results obtained support middle managers’ training in emotional competences through short, efficient, economic programs. Potential limitations and implications of the results are discussed (AU)

Antecedentes: este estudio se centra en la evaluación del Programa de Inteligencia Emocional Intensivo (PIEI; Fernández, 2016; Férreo, 2016) aplicado a supervisores de trabajo. El programa pretende incrementar la inteligencia emocional, ya que esta variable incide en aspectos como la satisfacción personal, el desempeño de tareas y el clima laboral. Método: la intervención se aplicó a supervisores de un gran call center, un sector poco estudiado en este ámbito. Participaron 282 supervisores pertenecientes a una empresa española multinacional, radicada en Madrid (51,4% varones y 48,6% mujeres). Fueron asignados, por disponibilidad, al grupo experimental (n = 190) o al grupo control (n = 92). Todos los supervisores respondieron a dos cuestionarios: uno para evaluar los componentes de inteligencia emocional intrapersonal (v.g., claridad, comprensión y reparación; TMMS-24; Fernández-Berrocal, Extremera y Ramos, 2004) y otro para medir empatía cognitiva y afectiva (v.g., adopción de perspectivas, comprensión emocional, alegría empática y estrés empático; TECA, López-Pérez, Fernández y Abad, 2008). Resultados: los resultados mostraron una mejora en las variables de estudio tras aplicar el programa en el grupo experimental. Conclusiones: los resultados obtenidos apoyan la formación emocional de mandos intermedios con programas breves, eficaces y económicos. Además, se discuten las limitaciones e implicaciones de los resultados obtenidos (AU)

Caracterización preliminar de la inmunidad pasiva natural en granjas porcicolas y evaluación de un sistema para incrementar la transferencia de anticuerpos / Preliminary characterization of the passive natural immunity in farms porcicolas and evaluation of a system to increase the transference of antibodies

Se determinó la transferencia pasiva de inmunidad natural en lechones de dos granjas porcícolas comerciales. Para ello se tomaron muestras de sangre a 221 lechones a las 24 horas de nacidos y a 21 cerdas madres. Los lechones de cada granja fueron divididos en dos grupos uno experimental y uno control. El primer grupo se manejo de acuerdo con las normas usuales para cada granja, mientras que a las madres de los lechones del segundo grupo se les aplicó un producto inmunomodulador a base de LPS y Propionibacterium granulosum. Los sueros obtenidos fueron analizados por las técnicas de electroforesis sobre acetato de celulosa, inmunoelectroforesis, inmunodifusión radial cuantitativa y prueba de turbidez con sulfato de Zinc. La concentración de proteína total fue determinada con el refractómetro de Golberg. Se analizan los resultados obtenidos y se discute la importancia de la adecuada transferencia pasiva de inmunidad natural y el posible uso del inmunomodulador en granjas comerciales con problemas de morbimortalidad neonatal.

Tratamento da hipersensibilidade dentinária avaliação de efetividade do uso do selante associado à água de hidróxido de cálcio / Dentinal hypersensitivity treatment: evaluation of the use of sealants associated with calcium hydroxid solution

A pesquisa avaliou a eficácia do selante e do hidróxido de cálcio no tratamento de dentes que apresentavam sensibilidade dentinária. Trinta e um (31) dentes receberam tratamento sendo divididos em dois grupos: Grupo I (somente selante) e Grupo II (selante e hidróxido de cálcio)