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

Farley, Scotland E.; Kyle, Jennifer E.; Leier, Hans C.; Bramer, Lisa M.; Weinstein, Jules B.; Bates, Timothy A.; Lee, Joon-Yong; Metz, Thomas O.; Schultz, Carsten; Tafesse, Fikadu G.

doi:10.1038/s41467-022-31097-7

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

Journal Article · Fri Jun 17 00:00:00 EDT 2022 · Nature Communications

DOI:https://doi.org/10.1038/s41467-022-31097-7· OSTI ID:1886312

Farley, Scotland E. ^[1]; ^[2]; Leier, Hans C. ^[1]; ^[2]; ^[1]; ^[1]; ^[2]; ^[2]; Schultz, Carsten ^[1]; ^[1]

Oregon Health & Science Univ., Portland, OR (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We find 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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); USDOE Laboratory Directed Research and Development (LDRD) Program

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1886312

Report Number(s):: PNNL-SA-165174

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 13; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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