IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-22166-4.html
   My bibliography  Save this article

SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition

Author

Listed:
  • Peter J. Mullen

    (University of California, Los Angeles (UCLA))

  • Gustavo Garcia

    (UCLA)

  • Arunima Purkayastha

    (UCLA)

  • Nedas Matulionis

    (University of California, Los Angeles (UCLA))

  • Ernst W. Schmid

    (University of California, Los Angeles (UCLA))

  • Milica Momcilovic

    (UCLA)

  • Chandani Sen

    (UCLA)

  • Justin Langerman

    (University of California, Los Angeles (UCLA))

  • Arunachalam Ramaiah

    (University of California, Irvine)

  • David B. Shackelford

    (UCLA
    UCLA)

  • Robert Damoiseaux

    (UCLA
    UCLA
    UCLA
    UCLA Samueli School of Engineering)

  • Samuel W. French

    (UCLA
    UCLA)

  • Kathrin Plath

    (University of California, Los Angeles (UCLA)
    UCLA
    UCLA
    UCLA)

  • Brigitte N. Gomperts

    (UCLA
    UCLA
    UCLA
    UCLA)

  • Vaithilingaraja Arumugaswami

    (UCLA
    UCLA)

  • Heather R. Christofk

    (University of California, Los Angeles (UCLA)
    UCLA
    UCLA)

Abstract

Viruses hijack host cell metabolism to acquire the building blocks required for replication. Understanding how SARS-CoV-2 alters host cell metabolism may lead to potential treatments for COVID-19. Here we profile metabolic changes conferred by SARS-CoV-2 infection in kidney epithelial cells and lung air-liquid interface (ALI) cultures, and show that SARS-CoV-2 infection increases glucose carbon entry into the TCA cycle via increased pyruvate carboxylase expression. SARS-CoV-2 also reduces oxidative glutamine metabolism while maintaining reductive carboxylation. Consistent with these changes, SARS-CoV-2 infection increases the activity of mTORC1 in cell lines and lung ALI cultures. Lastly, we show evidence of mTORC1 activation in COVID-19 patient lung tissue, and that mTORC1 inhibitors reduce viral replication in kidney epithelial cells and lung ALI cultures. Our results suggest that targeting mTORC1 may be a feasible treatment strategy for COVID-19 patients, although further studies are required to determine the mechanism of inhibition and potential efficacy in patients.

Suggested Citation

  • Peter J. Mullen & Gustavo Garcia & Arunima Purkayastha & Nedas Matulionis & Ernst W. Schmid & Milica Momcilovic & Chandani Sen & Justin Langerman & Arunachalam Ramaiah & David B. Shackelford & Robert , 2021. "SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22166-4
    DOI: 10.1038/s41467-021-22166-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-22166-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-22166-4?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
    ---><---

    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:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22166-4. 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.