Artículo
Effect of ivermectin and atorvastatin on nuclear localization of importin alpha and drug target expression profiling in host cells from nasopharyngeal swabs of sars‐cov‐2‐ positive patients
Segatori, Valeria Inés
; Garona, Juan
; Caligiuri, Lorena Grisel; Bizzotto, Juan Antonio
; Lavignolle, Rosario; Toro, Ayelén; Sanchis, Pablo Antonio
; Spitzer, Eduardo; Krolewiecki, Alejandro Javier
; Gueron, Geraldine
; Alonso, Daniel Fernando
Fecha de publicación:
10/2021
Editorial:
Multidisciplinary Digital Publishing Institute
Revista:
Viruses
ISSN:
1999-4915
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Nuclear transport and vesicle trafficking are key cellular functions involved in the pathogenesis of RNA viruses. Among other pleiotropic effects on virus‐infected host cells, ivermectin (IVM) inhibits nuclear transport mechanisms mediated by importins and atorvastatin (ATV) affects actin cytoskeleton‐dependent trafficking controlled by Rho GTPases signaling. In this work, we first analyzed the response to infection in nasopharyngeal swabs from SARS‐CoV‐2‐positive and ‐negative patients by assessing the gene expression of the respective host cell drug targets importins and Rho GTPases. COVID‐19 patients showed alterations in KPNA3, KPNA5, KPNA7, KPNB1, RHOA, and CDC42 expression compared with non‐COVID‐19 patients. An in vitro model of infection with Poly(I:C), a synthetic analog of viral double‐stranded RNA, triggered NF‐κB activation, an effect that was halted by IVM and ATV treatment. Importin and Rho GTPases gene expression was also impaired by these drugs. Furthermore, through confocal microscopy, we analyzed the effects of IVM and ATV on nuclear to cytoplasmic importin α distribution, alone or in combination. Results showed a significant inhibition of importin α nuclear accumulation under IVM and ATV treatments. These findings confirm transcriptional alterations in importins and Rho GTPases upon SARS‐CoV‐ 2 infection and point to IVM and ATV as valid drugs to impair nuclear localization of importin α when used at clinically‐relevant concentrations.
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Articulos(CCT - SALTA-JUJUY)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SALTA-JUJUY
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SALTA-JUJUY
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Segatori, Valeria Inés; Garona, Juan; Caligiuri, Lorena Grisel; Bizzotto, Juan Antonio; Lavignolle, Rosario; et al.; Effect of ivermectin and atorvastatin on nuclear localization of importin alpha and drug target expression profiling in host cells from nasopharyngeal swabs of sars‐cov‐2‐ positive patients; Multidisciplinary Digital Publishing Institute; Viruses; 13; 10; 10-2021
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