The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led society to live with a serious public health problem. In this sense, repositioning of antiretrovirals has captured the attention of the scientific community. Tenofovir disoproxil fumarate (TDF) is an antiretroviral compound that is used to treat acquired immune deficiency syndrome (AIDS) and hepatitis B. In this short report, we present a scale-up investigation of TDF by in situ infrared spectroscopy monitoring and a forced degradation study to describe a new degradation product. Finally, we have evaluated TDF in vitro for SARS-CoV-2 for the first time foreseeing the using of this medicine in pre-clinical and clinical investigations for the COVID-19 (coronavirus disease 2019) treatment.

Cell shape is regulated in Salmonella enterica serovar Typhimurium by complex mechanisms which coordinate growth with cell division and maintain bacillar cell shape through the whole cell cycle by controlling synthesis and degradation of cell envelope macromolecules. By using mecillinam, a β-lactam antibiotic that kills sensitive bacteria by interfering with the mechanisms regulating cell shape, it was demonstrated that genes controlling cell shape have an essential role since their inactivation was found to be lethal. Moreover, this lethality was conditional because it appeared only when growth proceeded on solid medium whereas growth in liquid medium was not affected. It was also found that many mutations which conferred resistance to mecillinam behaved as suppressors of that lethality. Among the genes concerned with mecillinam action, several related with global regulatory systems (cysB/cysE, cya/crp, spoT, LPS, mucM) were identifed. It was also demonstrated that some of those genes not only modifed the response to the antibiotic but also shown complex interactions with functions (slt, opgGH) related to the cell envelope.

En Salmonella enterica serovar Typhimurium (S. Typhimurium), la forma celular está controlada por complejos mecanismos que coordinan el crecimiento y la división celular, y mantienen durante el ciclo de vida la forma bacilar regulando la síntesis y degradación de las macromoléculas que constituyen la envoltura celular. Empleando mecilinam, un antibiótico β-lactámico de la familia de las penicilinas que debe su actividad bactericida a su capacidad para interferir con los mecanismos que regulan la forma celular, se han obtenido evidencias sobre el rol esencial de los genes que controlan la forma y se ha demostrado que la letalidad de las mutaciones que los afectan es condicional y se expresa cuando el crecimiento ocurre en medio sólido pero no en medio líquido. Se demostró, también, que muchas mutaciones que conferen resistencia a mecilinam actúan como supresoras de esa letalidad. Entre los genes cuya actividad condiciona la efectividad del antibiótico se identificaron varios relacionados con sistemas globales de regulación: cysB/cysE, cya/crp, spoT, LPS, mucM. Asimismo, se demostró que existen complejas interacciones entre esos genes, que modifican la respuesta al antibiótico y alteran funciones (slt, opgGH) relacionadas con la envoltura celular.