장연서 (서울대학교 의과대학)

조주연 (서울대학교 의과대학)

장연서 (서울대학교 의과대학)

조주연 (서울대학교 의과대학)

김혜란 (서울대학교 의과대학)

조남혁 (서울대학교 의과대학)

이욱비 (서울대학교 의과대학)

이재승 (서울대학교 의과대학)

Host metabolic reprogramming critically influences viral replication and disease progression during coronavirus infection. However, direct comparisons of SARS-CoV-2 and MERS-CoV under identical experimental conditions remain limited, particularly in lung tissue, the primary site of infection. Here, we performed integrated metabolomic, transcriptomic, and lipidomic analyses of lung tissues from SARS-CoV-2- or MERS-CoV-infected mice to define virus-specific host metabolic strategies.

SARS-CoV-2 induced pronounced activation of energy and amino acid metabolism during early infection, especially at 3 days post infection (DPI), followed by triacylglycerol accumulation and energy storage at 6 DPI. In contrast, MERS-CoV caused persistent alterations in lipid and nucleotide metabolism, with delayed lipid remodeling at 6 DPI. MERS-CoV also promoted sustained phospholipid- and sphingolipid-associated membrane remodeling together with stronger inflammatory transcriptomic responses.

These findings demonstrated that SARS-CoV-2 and MERS-CoV exploit host lipid metabolism through distinct, time-dependent programs in lung tissue. The results provided insight into their different disease trajectories and suggested that lipid-targeted antiviral strategies should account for both infection stage and virus-specific metabolic utilization patterns.