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

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. Here, Farley et al. perform untargeted lipidomics to assess how SARS-CoV-2 rewires host lipid metabolism. SARS-CoV-2 viral proteins specifically induce lipid droplet formation and dramatically change lipid metabolism to support infection; interfering with lipid metabolism using small molecule inhibitors decreases virus production.

Automated summary

A study using untargeted lipidomics reveals that SARS-CoV-2 infection rewires host lipid metabolism, leading to significant changes in lipid composition to support infection. The study also identifies lipid droplet plasticity as an important feature of infection and demonstrates that small-molecule glycerolipid biosynthesis inhibitors can block viral propagation.