IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v591y2021i7850d10.1038_s41586-021-03312-w.html
   My bibliography  Save this article

SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801

Author

Listed:
  • Angela Wahl

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Lisa E. Gralinski

    (University of North Carolina at Chapel Hill)

  • Claire E. Johnson

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Wenbo Yao

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Martina Kovarova

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Kenneth H. Dinnon

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Hongwei Liu

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Victoria J. Madden

    (University of North Carolina at Chapel Hill)

  • Halina M. Krzystek

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Chandrav De

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Kristen K. White

    (University of North Carolina at Chapel Hill)

  • Kendra Gully

    (University of North Carolina at Chapel Hill)

  • Alexandra Schäfer

    (University of North Carolina at Chapel Hill)

  • Tanzila Zaman

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Sarah R. Leist

    (University of North Carolina at Chapel Hill)

  • Paul O. Grant

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Gregory R. Bluemling

    (Emory University
    Drug Innovation Ventures at Emory (DRIVE))

  • Alexander A. Kolykhalov

    (Emory University
    Drug Innovation Ventures at Emory (DRIVE))

  • Michael G. Natchus

    (Drug Innovation Ventures at Emory (DRIVE))

  • Frederic B. Askin

    (University of North Carolina at Chapel Hill)

  • George Painter

    (Emory University
    Drug Innovation Ventures at Emory (DRIVE)
    Emory University)

  • Edward P. Browne

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Corbin D. Jones

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Raymond J. Pickles

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel)

  • Ralph S. Baric

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • J. Victor Garcia

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

Abstract

All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801—an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials—markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.

Suggested Citation

  • Angela Wahl & Lisa E. Gralinski & Claire E. Johnson & Wenbo Yao & Martina Kovarova & Kenneth H. Dinnon & Hongwei Liu & Victoria J. Madden & Halina M. Krzystek & Chandrav De & Kristen K. White & Kendra, 2021. "SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801," Nature, Nature, vol. 591(7850), pages 451-457, March.
    • Handle: RePEc:nat:nature:v:591:y:2021:i:7850:d:10.1038_s41586-021-03312-w
    DOI: 10.1038/s41586-021-03312-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03312-w
    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/s41586-021-03312-w?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. Haiqing Bai & Longlong Si & Amanda Jiang & Chaitra Belgur & Yunhao Zhai & Roberto Plebani & Crystal Yuri Oh & Melissa Rodas & Aditya Patil & Atiq Nurani & Sarah E. Gilpin & Rani K. Powers & Girija Goy, 2022. "Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Carolin M. Lieber & Robert M. Cox & Julien Sourimant & Josef D. Wolf & Kate Juergens & Quynh Phung & Manohar T. Saindane & Meghan K. Smith & Zachary M. Sticher & Alexander A. Kalykhalov & Michael G. N, 2022. "SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Nobuyo Higashi-Kuwata & Kohei Tsuji & Hironori Hayashi & Haydar Bulut & Maki Kiso & Masaki Imai & Hiromi Ogata-Aoki & Takahiro Ishii & Takuya Kobayakawa & Kenta Nakano & Nobutoki Takamune & Naoki Kish, 2023. "Identification of SARS-CoV-2 Mpro inhibitors containing P1’ 4-fluorobenzothiazole moiety highly active against SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-13, 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:591:y:2021:i:7850:d:10.1038_s41586-021-03312-w. 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.