IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v583y2020i7816d10.1038_s41586-020-2332-7.html
   My bibliography  Save this article

Proteomics of SARS-CoV-2-infected host cells reveals therapy targets

Author

Listed:
  • Denisa Bojkova

    (University Hospital Frankfurt, Goethe University)

  • Kevin Klann

    (Faculty of Medicine, Goethe University)

  • Benjamin Koch

    (University Hospital Frankfurt)

  • Marek Widera

    (University Hospital Frankfurt, Goethe University)

  • David Krause

    (Faculty of Medicine, Goethe University)

  • Sandra Ciesek

    (University Hospital Frankfurt, Goethe University
    External Partner Site Frankfurt)

  • Jindrich Cinatl

    (University Hospital Frankfurt, Goethe University)

  • Christian Münch

    (Faculty of Medicine, Goethe University
    Frankfurt Cancer Institute
    Cardio-Pulmonary Institute)

Abstract

A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV-2 in humans causes coronavirus disease 2019 (COVID-19) and has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses; however, treatment options and an understanding of how SARS-CoV-2 infects cells are lacking. Here we identify the host cell pathways that are modulated by SARS-CoV-2 and show that inhibition of these pathways prevents viral replication in human cells. We established a human cell-culture model for infection with a clinical isolate of SARS-CoV-2. Using this cell-culture system, we determined the infection profile of SARS-CoV-2 by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways such as translation, splicing, carbon metabolism, protein homeostasis (proteostasis) and nucleic acid metabolism. Small-molecule inhibitors that target these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and have enabled the identification of drugs that inhibit viral replication. We anticipate that our results will guide efforts to understand the molecular mechanisms that underlie the modulation of host cells after infection with SARS-CoV-2. Furthermore, our findings provide insights for the development of therapies for the treatment of COVID-19.

Suggested Citation

  • Denisa Bojkova & Kevin Klann & Benjamin Koch & Marek Widera & David Krause & Sandra Ciesek & Jindrich Cinatl & Christian Münch, 2020. "Proteomics of SARS-CoV-2-infected host cells reveals therapy targets," Nature, Nature, vol. 583(7816), pages 469-472, July.
    • Handle: RePEc:nat:nature:v:583:y:2020:i:7816:d:10.1038_s41586-020-2332-7
    DOI: 10.1038/s41586-020-2332-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-020-2332-7
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-020-2332-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jonas D. Albarnaz & Joanne Kite & Marisa Oliveira & Hanqi Li & Ying Di & Maria H. Christensen & Joao A. Paulo & Robin Antrobus & Steven P. Gygi & Florian I. Schmidt & Edward L. Huttlin & Geoffrey L. S, 2023. "Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Tabea M. Eser & Olga Baranov & Manuel Huth & Mohammed I. M. Ahmed & Flora Deák & Kathrin Held & Luming Lin & Kami Pekayvaz & Alexander Leunig & Leo Nicolai & Georgios Pollakis & Marcus Buggert & David, 2023. "Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Geng Liu & Wenya Du & Xiongbo Sang & Qiyu Tong & Ye Wang & Guoqing Chen & Yi Yuan & Lili Jiang & Wei Cheng & Dan Liu & Yan Tian & Xianghui Fu, 2022. "RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Sungmin Moon & Seunghan Han & In-Hwan Jang & Jaechan Ryu & Min-Seok Rha & Hyung-Ju Cho & Sang Sun Yoon & Ki Taek Nam & Chang-Hoon Kim & Man-Seong Park & Je Kyung Seong & Won-Jae Lee & Joo-Heon Yoon & , 2024. "Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Jack S. Gisby & Norzawani B. Buang & Artemis Papadaki & Candice L. Clarke & Talat H. Malik & Nicholas Medjeral-Thomas & Damiola Pinheiro & Paige M. Mortimer & Shanice Lewis & Eleanor Sandhu & Stephen , 2022. "Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    6. Yang Xu & Han Han & Ian Cooney & Yuxuan Guo & Noah G. Moran & Nathan R. Zuniga & John C. Price & Christopher P. Hill & Peter S. Shen, 2022. "Active conformation of the p97-p47 unfoldase complex," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    7. Kelsey M. Haas & Michael J. McGregor & Mehdi Bouhaddou & Benjamin J. Polacco & Eun-Young Kim & Thong T. Nguyen & Billy W. Newton & Matthew Urbanowski & Heejin Kim & Michael A. P. Williams & Veronica V, 2023. "Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    8. Emilie Murigneux & Laurent Softic & Corentin Aubé & Carmen Grandi & Delphine Judith & Johanna Bruce & Morgane Le Gall & François Guillonneau & Alain Schmitt & Vincent Parissi & Clarisse Berlioz-Torren, 2024. "Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:583:y:2020:i:7816:d:10.1038_s41586-020-2332-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.