Piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. In vitro antiviral activity evaluation against Zika and Dengue viruses.

Since 2011 Direct Acting antivirals (DAAs) drugs targeting different non-structural (NS) viral proteins (NS3, NS5A or NS5B inhibitors) have been approved for clinical use in HCV therapies. However, currently there are not licensed therapeutics to treat Flavivirus infections and the only licensed DENV vaccine, Dengvaxia, is restricted to patients with preexisting DENV immunity. Similarly to NS5 polymerase, the NS3 catalytic region is evolutionarily conserved among the Flaviviridae family sharing strong structural similarity with other proteases belonging to this family and therefore is an attractive target for the development of pan-flavivirus therapeutics. In this work we present a library of 34 piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. The library was developed through a privileged structures-based design and then biologically screened using a live virus phenotypic assay to determine the half-maximal inhibitor concentration (IC50) of each compound against ZIKV and DENV. Two lead compounds, 42 and 44, with promising broad-spectrum activity against ZIKV (IC50 6.6 µM and 1.9 µM respectively) and DENV (IC50 6.7 µM and 1.4 µM respectively) and a good security profile were identified. Besides, molecular docking calculations were performed to provide insights about key interactions with residues in NS3 proteases' active sites.

Estereotipos en cuidadores formales de personas mayores institucionalizadas en establecimientos de Montevideo, Uruguay / Stereotypes in formal caregivers of institutionalized elderly in long-stay centers in Montevideo, Uruguay

Objetivo: Describir el perfil sociolaboral y el nivel de estereotipos negativos acerca de la vejez en cuidadores formales de personas mayores, que trabajan en establecimientos de larga estancia en Montevideo, Uruguay. Metodología: Se contactaron 213 cuidadores formales pertenecientes a 80 establecimientos de Montevideo, a quienes se aplicó un cuestionario de datos sociolaborales y el cuestionario de estereotipos negativos sobre la vejez de Sánchez (2004). Resultados: El 95,3% son mujeres, con un promedio de 40 años, el 50,3% vive en pareja y el 65,3% con hijos a cargo. El 55,4% no accedió a formación específica. Niveles altos o muy altos de estereotipos se hallaron en el 68,8% para el test total, el 76,3% para el subfactor salud, el 59,2% para motivación-social y el 84,8% para carácter-personalidad. Conclusiones: La alta presencia de estereotipos tiene el potencial de generar peor calidad de la atención, perpetuando comportamientos y actitudes paternalistas e infantilizadoras que limitan el pleno ejercicio de derechos de los usuarios. Se hace necesario profundizar la formación profesional y desnaturalizar prácticas cotidianas de cuidado que podrían estar perpetuando los estereotipos (AU)

Objective: To describe the socio-occupational profile of formal caregivers and the level of negative stereotypes about the old age of these caregivers in Montevideo. Methodology: 213 formal caregivers belonging to 80 ELEPEM of Montevideo were contacted, to whom a questionnaire of socio-labor data and the Questionnaire of negative stereotypes on the old age of Sánchez (2004) were applied. Results: 95.3% are women, average 40 years old, 50.3% with a partner and 65.3% with dependent children. 55.4% did not access specific training. High or very high levels of stereotypes were found in 68.8% for the total test, 76.3% for the health subfactor, 59.2% for socialmotivation and 84.8% for personality character. Conclusions: The high presence of stereotypes has the potential to generate a poorer quality of care, perpetuating paternalistic and infantilizing behaviors and attitudes that limit the full exercise of users’ rights. It is necessary to deepen professional training and denature daily care practices that could be perpetuating stereotypes (AU)