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

Farley, S. E.; Kyle, J.; Leier, H.; Bramer, L. M.; Weinstein, J.; Bates, T. A.; Lee, J.-Y.; Metz, T. O.; Schultz, C.; Tafesse, F.

doi:10.1101/2022.02.14.480430

bioRxiv · 10.1101/2022.02.14.480430

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

Farley, S. E.·Kyle, J.·Leier, H.·Bramer, L. M.·Weinstein, J.·Bates, T. A.·Lee, J.-Y.·Metz, T. O.·Schultz, C.·Tafesse, F.

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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.

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Farley, S. E., Kyle, J., Leier, H., Bramer, L. M., Weinstein, J., Bates, T. A., Lee, J.-Y., Metz, T. O., Schultz, C., Tafesse, F.. 2022-02-15. A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants. https://doi.org/10.1101/2022.02.14.480430

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