Two synthetic steroid analogs reduce human respiratory syncytial virus replication and the immune response to infection both in vitro and in vivo

Carlos A Bueno; Franco M Salinas; L Vazquez; Laura E Alché; Flavia M Michelini

doi:10.1016/j.heliyon.2023.e20148

Two synthetic steroid analogs reduce human respiratory syncytial virus replication and the immune response to infection both in vitro and in vivo

Heliyon. 2023 Sep 26;9(10):e20148. doi: 10.1016/j.heliyon.2023.e20148. eCollection 2023 Oct.

Authors

Carlos A Bueno¹, Franco M Salinas¹, L Vazquez², Laura E Alché¹, Flavia M Michelini¹

Affiliations

¹ Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química Biológica (IQUIBICEN), Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina.
² UOCCB (Unidad Operativa Centro de Contención Biológica), Instituto Dr. Carlos G. Malbrán, ANLIS (Administración Nacional de Laboratorios e Institutos de Salud), Argentina.

Abstract

HRSV is responsible for many acute lower airway infections and hospitalizations in infants, the elderly and those with weakened immune systems around the world. The strong inflammatory response that mediates viral clearance contributes to pathogenesis, and is positively correlated with disease severity. There is no specific effective therapy on hand. Antiviral synthetic stigmastanes (22S, 23S)-22,23-dihydroxystigmast-4-en-3-one (Compound 1) and 22,23-dihydroxystigmasta-1,4-dien-3-one (Compound 2) have shown to be active inhibiting unrelated virus like Herpes Simplex type 1 virus (HSV-1) and Adenovirus, without cytotoxicity. We have also shown that Compound 1 modulates the activation of cell signaling pathways and cytokine secretion in infected epithelial cells as well as in inflammatory cells activated by nonviral stimuli. In the present work, we investigated the inhibitory effect of both compounds on HRSV replication and their modulatory effect on infected epithelial and inflammatory cells. We show that compounds 1 and 2 inhibit in vitro HRSV replication and propagation and reduce cytokine secretion triggered by HRSV infection in epithelial and inflammatory cells. The compounds reduce viral loads and inflammatory infiltration in the lungs of mice infected with HRSV.

Keywords: Anti-inflammatory; Antiviral; Human respiratory syncytial virus; Synthetic stigmastanes.