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Analysis of institutional authors

Tarrés-Freixas, FerranAuthorKochanowski, KarlAuthorVergara-Alert, JuliaAuthorSegales, JoaquimAuthor

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February 17, 2025
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Article

Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or m6A protein synthesis routes

Publicated to: Nature Communications. 16 (1): 1087- - 2025-02-07 16(1), DOI: 10.1038/s41467-025-56151-y

Authors: Molina, Elisa Molina; Bech-Serra, Joan Josep; Franco-Trepat, Eloi; Jarne, Ignasi; Perez-Zsolt, Daniel; Badia, Roger; Riveira-Munoz, Eva; Garcia-Vidal, Edurne; Revilla, Lluis; Franco, Sandra; Tarres-Freixas, Ferran; Roca, Nuria; Ceada, Gerardo; Kochanowski, Karl; Raich-Regue, Dalia; Erkizia, Itziar; Boreika, Rytis; Bordoy, Antoni E; Soler, Laia; Guil, Sonia; Carrillo, Jorge; Blanco, Julia; Martinez, Miguel angel; Paredes, Roger; Losada, Alejandro; Aviles, Pablo; Cuevas, Carmen; Vergara-Alert, Julia; Segales, Joaquim; Clotet, Bonaventura; Ballana, Ester; de la Torre, Carolina; Izquierdo-Useros, Nuria

Affiliations

Campus Univ Autonoma Barcelona UAB, Ctr Recerca Sanitat Anim CReSA, IRTA, Anim Hlth, Bellaterra 08193, Catalonia, Spain - Author
Campus Univ Autonoma Barcelona UAB, Ctr Recerca Sanitat Anim CReSA, Unitat Mixta Invest IRTA UAB Sanitat Anim, Bellaterra, Catalonia, Spain - Author
Case Western Reserve Univ, Ctr Global Hlth & Dis, Sch Med, Dept Pathol, Cleveland, OH 44106 USA - Author
Germans Trias i Pujol Univ Hosp, Infect Dis Dept, Badalona, Catalonia, Spain - Author
Germans Trias Pujol Res Inst & Hosp IGTP, Microbiol Dept, Badalona, Spain - Author
Inst Salud Carlos III, CIBER Enfermedades Infecciosas CIBERINFEC, Madrid, Spain - Author
Josep Carreras Leukaemia Res IJC, Barcelona, Spain - Author
Josep Carreras Leukaemia Res Inst IJC, Prote Unit, Badalona, Barcelona, Spain - Author
PharmaMar SA, Colmenar Viejo, Madrid, Spain - Author
Sanitat Animal. Producció Animal - Author
Univ Autonoma Barcelona, Fac Vet, Dept Sanitat & Anat Anim, Bellaterra, Barcelona, Spain - Author
Univ Autonoma Barcelona, Germans Trias & Pujol Res Inst IGTP, Badalona 08916, Spain - Author
Univ Vic Cent Univ Catalonia UVic UCC, Vic, Spain - Author
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Abstract

Plitidepsin is an antitumoral compound safe for treating COVID-19 that targets the translation elongation factor eEF1A. Here we detect that plitidepsin decreases de novo cap-dependent translation of SARS-CoV-2 and non-viral RNAs but affects less than 13% of the host proteome, thus preserving cellular viability. In response to plitidepsin, cells upregulate EIF2AK3 and proteins that reduce translation, but also proteins that support proteostasis via ribosome synthesis and cap-independent translation by eIF4G2 and IGF2BP2. While plitidepsin inhibits cap- or internal ribosome entry sites (IRES)-mediated translation, its impact on N6-methyladenosine (m6A) translation is limited. In agreement, plitidepsin blocks members of Coronaviridae, Flaviviridae, Pneumoviridae and Herpesviridae families. Yet, it fails to inhibit retroviruses that exploit m6A synthesis routes and are blocked by drugs targeting IGF2BP2 m6A reader. By deciphering the molecular fingerprint of cells treated with therapies targeting translation we identify a rational approach to select broad-spectrum antivirals with potential to counteract future pandemic viruses.

Keywords

AdenosineAntiviral agentsC-virus-rnaCellCovid-19Covid-19 drug treatmentEef1a1 protein, humanEfficientEukaryotic initiation factor-4gHek293 cellsHost-directed therapiesHumansInhibitionInternal ribosome entry sitesPeptide elongation factor 1Peptides, cyclicPlitidepsinProtein biosynthesisReplicationRna capsSars-cov-2

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Communications due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 10/135, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-13:

  • WoS: 6

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-13:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 17.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 18 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 30.
  • The number of mentions on the social network X (formerly Twitter): 13 (Altmetric).
  • The number of mentions in news outlets: 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/20.500.12327/3715

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United States of America.

Observations

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/; MICINN/Programa Estatal para impulsar la Investigación Científico-Técnica y su Transferencia/PID2023-147498OB-I00/ES/NUEVAS TERAPIAS ANTIVIRALES E INMUNOMODULADORAS DE AMPLIO ESPECTRO FRENTE A FACTORES CELULARES DEL HUESPED/; EU/H2020/101046118/EC/RBD Dimer recombinant protein vaccine against SARSCoV2/RBDCOV; MICINN/ /JDC2023-050389-I/ES/ /; MICINN/Programa Estatal para Desarrollar, Atraer y Retener Talento/RYC2021-033035-I/ES/ /; MICINN/ /PLEC2022-009171/ES/Granja in vitro: desarrollo del primer biobanco de organoides de animales de granja como alternativa a los experimentos con animales en la investigación de enfermedades infecciosas/FARMBANK

Awards linked to the item

N.I-U. is supported by the Spanish Ministry of Science and Innovation (grants PID2020-117145RB-I00, PID2023-147498OB-I00 and 10.13039/501100011033, Spain), EU HORIZON-HLTH-2021CORONA-01 (grant 101046118, European Union) and by institutional funding of PharmaMar, Grifols, HIPRA, and Amassence. E.M-M. is supported by the Spanish Ministry of Science and Innovation (grant PRE2021-099271). E.F-T is supported by JDC2023-050389-I funded by MCIU/AEI/10.13039/501100011033 and FSE+. E.G-V. is a research fellow from PERIS (SLT017/20/000090). E.B. and R.B. are research fellows from ISCIII-FIS (CPII19/00012; CP19/00011). K.K. is supported by funding from the Spanish Ministry of Research and Innovation (RYC2021-033035-I/AEI/10.13039/501100011033). G.C. is supported with funding from PLEC2022-009171/AEI/10.13039/501100011033. IrsiCaixa is supported by 2021 SGR 0045. The proteomic analyses were conducted at the IJC Proteomics Unit, which is affiliated with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Spanish Platform of Molecular and Bioinformatics Resources (ProteoRed), Instituto de Salud Carlos III (PT17/0019), and CERCA GINYNS. This unit serves as a gateway to scientific and technical infrastructures. We acknowledge J. Diaz from the CMCiB for his constant help at the BSL3 facility. We thank the contribution of E. Martro and V. Saludes from the Microbiology department of HUGTIP for their constant help to identify and sequence SARS-CoV-2 variants. The authors also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com) and Foundation Dormeur for financial support for the acquisition of the QuantStudio-5 real-time PCR system and an Eclipse Ts2RFL inverted research microscope.