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

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

doi:10.1038/s41467-022-31097-7

Cited by 31 publications

(32 citation statements)

References 76 publications

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“…Supplementation of saturated PA and unsaturated OA and LA in the condition of FFA deficiency has been reported to restore the replication of not only RNA viruses including not only SARS-CoV-2, IAV, MERS-CoV, and enterovirus but also DNA viruses such as adenovirus. 11 , 15 In agreement with previous studies, 11 , 15 supplementation of FFAs during FFA deficiency by lipase inhibitors was found to rescue the replication of SARS-CoV-2 and IAV. The addition of unsaturated FFAs such as LA and OA at the time of virus inoculation is known to inhibit pathogenic human β-coronaviruses through their binding to FFA binding pocket in the spike protein, which blocks virus entry.…”

Section: Discussionsupporting

confidence: 89%

“…2k, l ), an observation consistent with the previous reports. 11 , 15 Furthermore, siRNA-mediated gene silencing of ATGL and/or HSL markedly suppressed the protein expression levels of hemagglutinin (HA) and M2 (active as an ion channel 16 ), genome replication, and infectious progeny production through inhibition of LD degradation in IAV-infected A549 cells (Fig. 2m–p ).…”

Section: Resultsmentioning

confidence: 93%

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Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus

Baek

Kwon

Sharif

et al. 2022

Sig Transduct Target Ther

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The biosynthesis of host lipids and/or lipid droplets (LDs) has been studied extensively as a putative therapeutic target in diverse viral infections. However, directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated. Here, we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids (FFAs) at the late stage of diverse RNA viral infections, which represents a broad-spectrum antiviral target. Dysfunction of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection, thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of energy. The replication of SARS-CoV-2 and influenza A virus (IAV), which is suppressed by the treatment with LD-associated lipases inhibitors, is rescued by supplementation with FFAs. The administration of lipase inhibitors, either individually or in a combination with virus-targeting drugs, protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected hamsters. Moreover, the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2- and IAV-challenged animals, a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV patients. In conclusion, the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19- and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 93%

Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus

Baek

Kwon

Sharif

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

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“… 38 Studies also suggest substantial changes in oral and gut microbiome and proteomic and metabolomic profiles of individuals infected with SARS-CoV-2 that could last well beyond the acute phase and contribute to changes in lipid profiles. 1 , 2 , 3 , 4 , 5 , 37 , 38 , 39 , 40 Behavioural changes, such as a change in diet and exercise, other COVID-19 pandemic stressors (including lockdowns, social isolation, and loneliness), grief, and other stressors might have differentially affected people with COVID-19 and could also be responsible for some of the effect seen here. We observed a higher risk of an increase in BMI in people with COVID-19 versus both the contemporary and historical controls; the extent to which this increase in BMI following SARS-CoV-2 infection might mediate incident dyslipidaemia or whether, conversely, occurrence of dyslipidaemia following infection might mediate the increase in BMI will need to be examined in future studies.…”

Section: Discussionmentioning

confidence: 89%

Risks and burdens of incident dyslipidaemia in long COVID: a cohort study

Xie

Al‐Aly

2023

The Lancet Diabetes & Endocrinology

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“…1 , 2 , 3 ). A lipidomics study has also shown that there are no differences in lipid profiles in patients infected with different virus variants (Farley et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A metabolic readout of the urine metabolome of COVID-19 patients

et al. 2023

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Analysis of urine samples from COVID-19 patients by 1 H NMR reveals important metabolic alterations due to SAR-CoV-2 infection. Previous studies have identified biomarkers in urine that reflect metabolic alterations in COVID-19 patients. We have used 1 H NMR to better define these metabolic alterations since this technique allows us to obtain a broad profile of the metabolites present in urine. This technique offers the advantage that sample preparation is very simple and gives us very complete information on the metabolites present. To detect these alterations, we have compared urine samples from COVID-19 patients (n = 35) with healthy people (n = 18). We used unsupervised (Robust PCA) and supervised (PLS-LDA) multivariate analysis methods to evaluate the differences between the two groups: COVID-19 and healthy controls. The differences focus on a group of metabolites related to energy metabolism (glucose, ketone bodies, glycine, creatinine, and citrate) and other processes related to bacterial flora (TMAO and formic acid) and detoxification (hippuric acid). The alterations in the urinary metabolome shown in this work indicate that SARS-CoV-2 causes a metabolic change from a normal situation of glucose consumption towards a gluconeogenic situation and possible insulin resistance. Supplementary Information The online version contains supplementary material available at 10.1007/s11306-023-01971-6.

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

Cited by 31 publications

References 76 publications

Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus

Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus

Risks and burdens of incident dyslipidaemia in long COVID: a cohort study

A metabolic readout of the urine metabolome of COVID-19 patients

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