Unraveling the antiviral activity of plitidepsin against SARS-CoV-2 by subcellular and morphological analysis

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. Pli...

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Bibliographic Details
Authors: Sachse, Martin, Tenorio, Raquel, Fernández de Castro, Isabel, Muñoz-Basagoiti, Jordana|||0000-0002-0384-5928, Perez-Zsolt, Daniel|||0000-0003-4192-7622, Raïch-Regué, Dàlia|||0000-0001-7656-5700, Rodon, Jordi|||0000-0002-1032-9091, Losada, Alejandro, Avilés, Pablo, Cuevas, Carmen, Paredes, Roger|||0000-0002-6553-691X, Segalés Coma, Joaquim|||0000-0002-1539-7261, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Vergara-Alert, Júlia|||0000-0001-7484-444X, Izquierdo Useros, Nuria|||0000-0002-1039-1821, Risco, Cristina|||0000-0001-7501-5934
Format: article
Publication Date:2022
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:257282
Online Access:https://ddd.uab.cat/record/257282
https://dx.doi.org/urn:doi:10.1016/j.antiviral.2022.105270
Access Level:Open access
Keyword:Antiviral
Covid-19
Electron microscopy
Plitidepsin
SARS-CoV-2
Description
Summary: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.

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