Coronavirus Infection and Cholesterol Metabolism

Dai, Jun; Wang, Huan; Liao, Ying; Tan, Lei; Sun, Yingjie; Chen, Song; Liu, Weiwei; Qiu, Xusheng; Ding, Chan

doi:10.3389/fimmu.2022.791267

Cited by 33 publications

(25 citation statements)

References 257 publications

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“…A redox imbalance can explain the individual variability of COVID-19. Coronaviruses exploit a host’s cholesterol metabolism to accommodate viral replication requirements and interfere with the host’s immune responses [ 41 ]. An in vitro study shows the inhibitory activity of the redox active oxysterol 27-hydroxycholesterol (27-HC) against SARS-CoV-2 without significant cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of HDL-C on long-term mortality in patients with COVID-19 pneumonia in the Turkish population: A potential mechanism for population differences

Baycan¹,

Bölen²,

Atalay³

et al. 2022

Bosn J of Basic Med Sci

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Coronavirus disease 2019 (COVID-19) is diagnosed by the evidence of the presence of multiple phenotypes, including thrombosis, inflammation, and alveolar and myocardial damage, which can cause severe illness and mortality. High-density lipoprotein cholesterol (HDL-C) has pleiotropic properties, including anti-inflammatory, anti-infectious, antithrombotic, and endothelial cell protective effects. The aim of this study was to investigate the HDL-C levels and one-year mortality after the first wave of patients with COVID-19 were hospitalized. Data from 101 patients with COVID-19 were collected for this single-center retrospective study. Lipid parameters were collected on the admission. The relationship between lipid parameters and long-term mortality was investigated. The mean age of the non-survivor group (n = 38) was 68.8 ± 14.1 years, and 55% were male. The HDL-C levels were significantly lower in the non-survivors group compared with the survivors (26.9 ± 9.5 vs 36.8 ± 12.8 mg/dl, respectively p < 0.001). Multivariate regression analysis determined that age, C-reactive protein, D-dimer, hypertension, and HDL-C as independent predictors for the development of COVID-19 mortality. HDL-C levels <30.5 mg/dl had 71% sensitivity and 68% specificity to predict one-year mortality after COVID-19. The findings of this study showed that HDL-C is a predictor of one-year mortality in Turkish patients with COVID-19. COVID-19 is associated with decreased lipid levels, and it is an indicator of the inflammatory burden and increased mortality rate. The consequences of long-term metabolic dysregulations in patients that have recovered from COVID-19 still need to be understood.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of HDL-C on long-term mortality in patients with COVID-19 pneumonia in the Turkish population: A potential mechanism for population differences

Baycan¹,

Bölen²,

Atalay³

et al. 2022

Bosn J of Basic Med Sci

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“…A strong relationship between cholesterol and coronavirus replication has been widely documented in the literature (Thorp and Gallagher, 2004;Syed et al, 2010;Heaton and Randall, 2011;Blanc et al, 2013;Del Campo and Romero-Goḿez, 2015;Guo et al, 2017;Meher et al, 2019;Lange et al, 2019;Cao et al, 2020;Radenkovic et al, 2020;Balgoma et al, 2020;Luquain-Costaz et al, 2020;Sanders et al, 2021;Cheng et al, 2021). Our previous study has also shown that cholesterol has an important role in coronavirus entry, membrane fusion and pathological syncytia formation; therefore cholesterol metabolic mechanisms may be promising drug targets for coronavirus infections (Dai et al, 2022). Herein, we obtained the gene expression profiles of DF-1 cells exposed to Dex for 24 h, and the RNA-seq data indicated that many genes associated with cholesterol biosynthesis were up-regulated by Dex.…”

Section: Discussionmentioning

confidence: 64%

Non-Targeted Metabolomic Analysis of Chicken Kidneys in Response to Coronavirus IBV Infection Under Stress Induced by Dexamethasone

Dai

Wang

Liao

et al. 2022

Front. Cell. Infect. Microbiol.

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Stress in poultry can lead to changes in body metabolism and immunity, which can increase susceptibility to infectious diseases. However, knowledge regarding chicken responses to viral infection under stress is limited. Dexamethasone (Dex) is a synthetic glucocorticoid similar to that secreted by animals under stress conditions, and has been widely used to induce stress in chickens. Herein, we established a stress model in 7-day-old chickens injected with Dex to elucidate the effects of stress on IBV replication in the kidneys. The metabolic changes, immune status and growth of the chickens under stress conditions were comprehensively evaluated. Furthermore, the metabolic profile, weight gain, viral load, serum cholesterol levels, cytokines and peripheral blood lymphocyte ratio were compared in chickens treated with Dex and infected with IBV. An LC-MS/MS-based metabolomics method was used to examine differentially enriched metabolites in the kidneys. A total of 113 metabolites whose abundance was altered after Dex treatment were identified, most of which were lipids and lipid-like molecules. The principal metabolic alterations in chicken kidneys caused by IBV infection included fatty acid, valine, leucine and isoleucine metabolism. Dex treatment before and after IBV infection mainly affected the host’s tryptophan, phenylalanine, amino sugar and nucleotide sugar metabolism. In addition, Dex led to up-regulation of serum cholesterol levels and renal viral load in chickens, and to the inhibition of weight gain, peripheral blood lymphocytes and IL-6 production. We also confirmed that the exogenous cholesterol in DF-1 cells promoted the replication of IBV. However, whether the increase in viral load in kidney tissue is associated with the up-regulation of cholesterol levels induced by Dex must be demonstrated in future experiments. In conclusion, chick growth and immune function were significantly inhibited by Dex. Host cholesterol metabolism and the response to IBV infection are regulated by Dex. This study provides valuable insights into the molecular regulatory mechanisms in poultry stress, and should support further research on the intrinsic link between cholesterol metabolism and IBV replication under stress conditions.

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“…Different papers reported that the virus is using the cholesterol to invade the cell. SARS-CoV-2 infection was also reported to cause lower serum cholesterol levels in COVID-19 patients (reviewed in 57 ). Our experiments demonstrate that pantethine reduces cellular cholesterol levels.…”

Section: Discussionmentioning

confidence: 99%

Potential antiviral effects of pantethine against SARS-CoV-2

Abou-Hamdan

Saleh

Mani

et al. 2023

Sci Rep

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SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection, in Vero E6 cells and in Calu-3a cells. Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.

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Coronavirus Infection and Cholesterol Metabolism

Cited by 33 publications

References 257 publications

Prognostic significance of HDL-C on long-term mortality in patients with COVID-19 pneumonia in the Turkish population: A potential mechanism for population differences

Prognostic significance of HDL-C on long-term mortality in patients with COVID-19 pneumonia in the Turkish population: A potential mechanism for population differences

Non-Targeted Metabolomic Analysis of Chicken Kidneys in Response to Coronavirus IBV Infection Under Stress Induced by Dexamethasone

Potential antiviral effects of pantethine against SARS-CoV-2

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