Unraveling the antiviral activity of plitidepsin against SARS-CoV-2 by subcellular and morphological analysis
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Autor/a
Sachse, Martin
Tenorio, Raquel
Fernández de Castro, Isabel
Muñoz-Basagoiti, Jordana
Perez-Zsolt, Daniel
Raïch-Regué, Dàlia
Rodon, Jordi
Losada, Alejandro
Avilés, Pablo
Cuevas, Carmen
Paredes, Roger
Clotet, Bonaventura
Vergara-Alert, Júlia
Izquierdo-Useros, Nuria
Risco, Cristina
Fecha de publicación
2022-02-26ISSN
0166-3542
Resumen
The pandemic caused by the new coronavirus SARS-CoV-2 has made evident the need for broad-spectrum, efficient antiviral treatments to combat emerging and re-emerging viruses. Plitidepsin is an antitumor agent of marine origin that has also shown a potent pre-clinical efficacy against SARS-CoV-2. Plitidepsin targets the host protein eEF1A (eukaryotic translation elongation factor 1 alpha) and affects viral infection at an early, post-entry step. Because electron microscopy is a valuable tool to study virus-cell interactions and the mechanism of action of antiviral drugs, in this work we have used transmission electron microscopy (TEM) to evaluate the effects of plitidepsin in SARS-CoV-2 infection in cultured Vero E6 cells 24 and 48h post-infection. In the absence of plitidepsin, TEM morphological analysis showed double-membrane vesicles (DMVs), organelles that support coronavirus genome replication, single-membrane vesicles with viral particles, large vacuoles with groups of viruses and numerous extracellular virions attached to the plasma membrane. When treated with plitidepsin, no viral structures were found in SARS-CoV-2-infected Vero E6 cells. Immunogold detection of SARS-CoV-2 nucleocapsid (N) protein and double-stranded RNA (dsRNA) provided clear signals in cells infected in the absence of plitidepsin, but complete absence in cells infected and treated with plitidepsin. The present study shows that plitidepsin blocks the biogenesis of viral replication organelles and the morphogenesis of virus progeny. Electron microscopy morphological analysis coupled to immunogold labeling of SARS-CoV-2 products offers a unique approach to understand how antivirals such as plitidepsin work.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
619 - Veterinaria
Páginas
9
Publicado por
Elsevier
Publicado en
Antiviral Research
Citación
Sachse, Martin, Raquel Tenorio, Isabel Fernández de Castro, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Dàlia Raïch-Regué, Jordi Rodon, Alejandro Losada, Pablo Avilés, Carmen Cuevas, Roger Paredes, Joaquim Segalés, Bonaventura Clotet, Júlia Vergara-Alert, Nuria Izquierdo-Useros, and Cristina Risco. 2022. "Unraveling The Antiviral Activity Of Plitidepsin Against SARS-Cov-2 By Subcellular And Morphological Analysis". Antiviral Research 200: 105270. doi:10.1016/j.antiviral.2022.105270.
Número del acuerdo de la subvención
MICIU/Programa Estatal de I+D+I orientada a los retos de la sociedad/RTI2018-094445-B-I00/ES/BUSQUEDA DE NUEVOS ANTIVIRALES DE AMPLIO ESPECTRO: TRANSPORTE DE LIPIDOS Y PROTEINAS MITOCONDRIALES COMO DIANAS/
MICINN/Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-117145RB-I00/ES/NUEVAS TERAPIAS ANTIVIRALES E INMUNOMODULADORAS FRENTE AL SARS-COV-2/
Program
Sanitat Animal
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