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

Autor:	Bueno CA; 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., Salinas FM; 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., Vazquez L; UOCCB (Unidad Operativa Centro de Contención Biológica), Instituto Dr. Carlos G. Malbrán, ANLIS (Administración Nacional de Laboratorios e Institutos de Salud), Argentina., Alché LE; 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., Michelini FM; 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.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2023 Sep 26; Vol. 9 (10), pp. e20148. Date of Electronic Publication: 2023 Sep 26 (Print Publication: 2023).
DOI:	10.1016/j.heliyon.2023.e20148
Abstrakt:	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. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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