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A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants

Scotland E. Farley, Jennifer E. Kyle, Hans C. Leier, Lisa M. Bramer, Jules Weinstein, Timothy A. Bates, Joon-Yong Lee, Thomas O. Metz, Carsten Schultz, View ORCID ProfileFikadu G. Tafesse
doi: https://doi.org/10.1101/2022.02.14.480430
Scotland E. Farley
1Department of Molecular Microbiology & Immunology. Oregon Health & Science University; Portland, OR, USA
4Department of Chemical Physiology and Biochemistry. Oregon Health & Science University; Portland, OR, USA
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Jennifer E. Kyle
2Biological Sciences Division, Earth and Biological Sciences Directorate. Pacific Northwest National Laboratory (PNNL); Richland, WA, USA
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Hans C. Leier
1Department of Molecular Microbiology & Immunology. Oregon Health & Science University; Portland, OR, USA
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Lisa M. Bramer
3Computational Biology Group, Biological Sciences Division, Earth & Biological Systems Directorate. PNNL; Richland, WA, USA
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Jules Weinstein
1Department of Molecular Microbiology & Immunology. Oregon Health & Science University; Portland, OR, USA
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Timothy A. Bates
1Department of Molecular Microbiology & Immunology. Oregon Health & Science University; Portland, OR, USA
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Joon-Yong Lee
2Biological Sciences Division, Earth and Biological Sciences Directorate. Pacific Northwest National Laboratory (PNNL); Richland, WA, USA
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Thomas O. Metz
2Biological Sciences Division, Earth and Biological Sciences Directorate. Pacific Northwest National Laboratory (PNNL); Richland, WA, USA
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Carsten Schultz
4Department of Chemical Physiology and Biochemistry. Oregon Health & Science University; Portland, OR, USA
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Fikadu G. Tafesse
1Department of Molecular Microbiology & Immunology. Oregon Health & Science University; Portland, OR, USA
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  • ORCID record for Fikadu G. Tafesse
  • For correspondence: tafesse@ohsu.edu
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Abstract

A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. We mapped alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We found that SARS-CoV-2 rewires host lipid metabolism, altering 409 lipid species up to 64-fold relative to controls. We correlated these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We found that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We found that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 15, 2022.
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A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Scotland E. Farley, Jennifer E. Kyle, Hans C. Leier, Lisa M. Bramer, Jules Weinstein, Timothy A. Bates, Joon-Yong Lee, Thomas O. Metz, Carsten Schultz, Fikadu G. Tafesse
bioRxiv 2022.02.14.480430; doi: https://doi.org/10.1101/2022.02.14.480430
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A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Scotland E. Farley, Jennifer E. Kyle, Hans C. Leier, Lisa M. Bramer, Jules Weinstein, Timothy A. Bates, Joon-Yong Lee, Thomas O. Metz, Carsten Schultz, Fikadu G. Tafesse
bioRxiv 2022.02.14.480430; doi: https://doi.org/10.1101/2022.02.14.480430

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