bims-mevinf 2025-07-20 papers

J Lipid Res. 2025 Jul 12. pii: S0022-2275(25)00122-1. [Epub ahead of print] 100860

Integrated lipidomic and proteomic profiling reveals metabolic network disruption by SARS-CoV-2 variants.

Scotland E Farley, Jennifer E Kyle, Helene Jahn, Lisa M Bramer, Paul D Piehowski, Athena A Shepmoes, Brooke Ld Kaiser, Sarai M Williams, Josie G Eder, Carsten Schultz, Fikadu G Tafesse.

The rapid evolution of SARS-CoV-2 has produced myriad viral strains with increasing transmissibility and capacity for immune evasion. While effective vaccination campaigns have reduced the fatalities associated with SARS-CoV-2, infections continue, and a detailed understanding of how this virus manipulates host biochemical pathways remains elusive. We asked both whether the patterns of host lipid rewiring remained consistent across variants and whether the changes in the abundance of lipid classes are related to changes in the expression of the enzymes involved in their biosynthesis. We compared global nontargeted lipidomics on A549-ACE2 cells infected with the delta variant (B.1.617.2), or the omicron (B.1.1.529) variant to our previous results of global nontargeted lipidomics on A549-ACE2 cells infected with the original WA1 strain, and further performed quantitative proteomics to assess changes in the host proteome. We found that metabolic rewiring, both on the lipid and the enzymatic level, is remarkably consistent across all three variants. We further mapped changes in the expression of host metabolic enzymes, linking enzyme expression to alterations in the abundance of specific lipids during infection. This analysis identified key proteins related to virus-mediated changes in lipid abundance, including fatty acid synthase (FASN), lysosomal acid lipase (LIPA), and ORMDL, a regulator of sphingolipid biosynthesis. These integrated lipidomic and proteomic experiments shed light on the importance of the complex network of host metabolism networks that support SARS-CoV-2 infection, and suggest that lipid metabolism may be a promising avenue for uncovering conserved therapeutic targets.

Keywords: SARS-CoV-2; SARS-CoV-2 variants; ceramides; coronavirus; host-virus interaction; lipid metabolism; lipidomics; neutral lipids; proteomics; sphingolipids

DOI: https://doi.org/10.1016/j.jlr.2025.100860

Virulence. 2025 Dec;16(1): 2532806

A comprehension and systematic insight into the interaction between ferroptosis and virus infection: The implications of mechanisms and strategies.

Sai Niu, Yian Deng, Yonggen Yang, Junjie Wang, Chunyue Fang, Ying Zhou, Hanchuan Dai.

Ferroptosis is a novel form of iron-dependent programmed cell death characterized by iron metabolic derangement, an abnormal antioxidant system, and lipid peroxidation. Emerging evidence revealed that viruses modulate ferroptosis to facilitate their replication, dissemination, and pathogenesis, thereby promoting infection or achieving immune evasion by hijacking the host's iron metabolism. However, the interplay between ferroptosis and virus infections remains to be elucidated. This review comprehensively summarizes the core mechanisms of ferroptosis, including iron homeostasis, the system Xc-/GPX4 pathway, the FSP1/CoQ10 pathway, lipid peroxidation, and their essential roles were discussed in ferroptosis. We highlighted the relationship between the core mechanisms of ferroptosis and virus infection. Furthermore, we revealed the underlying pathogenic mechanisms of viral infections and the prospective applications targeting ferroptosis. This article is conducive to deepening our understanding of the regulatory mechanism of ferroptosis, unraveling the potential therapeutic intervention and pharmacological direction for the development of innovative ferroptosis-dependent antiviral agents.

Keywords: Cell death; Ferroptosis; iron metabolism; lipid peroxidation; virus infection

DOI: https://doi.org/10.1080/21505594.2025.2532806

BMC Gastroenterol. 2025 Jul 16. 25(1): 523

Interferon therapy for chronic hepatitis B virus infection affects nucleoside metabolism: a metabolomics study.

Xiangyang Ye, Rongxian Qiu, Xiongzhi He, Zhenting Hu, Fengfeng Zheng, Xiaogang Huang, Xuemei Xie, Feihua Chen, Hanbing Ou.

Keywords: Hepatitis B virus; Interferon treatment; Metabolomics; Methylated modification; Nucleoside metabolism

DOI: https://doi.org/10.1186/s12876-025-04126-0

iScience. 2025 Jul 18. 28(7): 112925

NRF2 regulates lipid droplet dynamics to prevent lipotoxicity.

Christopher T Prevost, William B Gansereit, David F Kashatus.

Lipid droplets (LDs) are dynamic organelles comprising a neutral lipid core encapsulated by a phospholipid monolayer. LD structure and function are influenced by a variety of intrinsic and extrinsic signals, and cells alter LD content and distribution to adapt to their environment. Here, we show that LD content increases in response to stabilization of the transcription factor NRF2 under conditions of lipotoxic stress. Notably, NRF2 activity leads to increased expression of the G0S2, a protein that inhibits ATGL, the enzyme responsible for degradation of triacylglycerol and the release of fatty acids from LDs. Importantly, stabilization of NRF2 in the absence of stress is sufficient to increase LD content, and inhibition of ATGL partially rescues the impact of NRF2 deletion on stress-induced ferroptosis. These data support a model in which stress-induced NRF2 stabilization protects cells against lipotoxicity in part through the sequestration of fatty acids in lipid droplets.

Keywords: Biochemistry; Biological sciences; Cell biology

DOI: https://doi.org/10.1016/j.isci.2025.112925

bioRxiv. 2025 May 02. pii: 2025.05.02.651833. [Epub ahead of print]

Auranofin Inhibits Hepatitis E Virus Replication Via Reactive Oxygen Species.

Kateland Tiller, S Tyler Williams, Bo Wang, Debin Tian, Xiang-Jin Meng, James Weger-Lucarelli.

Hepatitis E virus (HEV) causes roughly 20 million yearly global infections, and is associated with chronic hepatitis, neurological sequelae and pregnancy-related adverse outcomes that require antiviral therapeutic intervention. While there are currently no approved HEV-specific therapeutics, ribavirin and pegylated interferon, prescribed off-label, are the current standard of care. However, ribavirin resistance and toxicity highlight the unmet clinical need to identify safer, HEV-specific antivirals. Auranofin, an FDA-approved anti-rheumatic drug, displays antiviral activity against several viruses. Therefore, we investigated auranofin's potential as an antiviral and its mechanism of action against HEV. We demonstrated that auranofin displays dose-dependent antiviral activity against two genotypes of HEV that cause a significant proportion of human disease, as well as against a ribavirin treatment failure-associated mutant. Because auranofin is known to increase reactive oxygen species (ROS), we investigated the antiviral mechanism of action via treatment with ROS inhibitors. ROS inhibitors reversed auranofin-mediated ROS promotion and antiviral activity, suggesting the observed antiviral effects are mediated by ROS. Furthermore, treatment with a different ROS promotor, D-amino acid oxidase (DAAO), also displays antiviral activity against HEV, which was also reversed by treatment with a ROS inhibitor, suggesting that ROS accumulation alone is antiviral. We also demonstrated that combined treatment with auranofin and ribavirin exhibits synergistic antiviral activity in vitro , which supports repurposing auranofin as an antiviral against HEV, potentially in combination with ribavirin. Overall, this study has important implications in repurposing auranofin as an antiviral against HEV and in delineating the mechanism of action against HEV via ROS.
Importance: Hepatitis E virus (HEV) lacks approved antiviral therapies, and off-label treatments are limited by toxicity and emerging resistance. This study identifies the FDA-approved drug auranofin as an effective in vitro inhibitor of HEV, including two globally relevant human-associated genotypes and a ribavirin treatment failure-associated mutant. Auranofin's activity highlights the therapeutic potential of host-targeting antivirals, particularly those that promote the generation of reactive oxygen species, in treating HEV infection. These findings support further in vivo investigations of auranofin as a treatment for HEV and suggest that modulating host redox pathways by promoting reactive oxygen species may represent a promising strategy for broad-spectrum antiviral development.

DOI: https://doi.org/10.1101/2025.05.02.651833