SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, endoplasmic reticulum stress and DNA synthesis

Wang, Yijun; Huang, Jinbao; Sun, Yong; He, Jun; Li, Weiwei; Liu, Zhongfan; Taylor, Ethan Will; Rayman, Margaret P.; Wan, Xiaochun; Zhang, Jinsong

doi:10.1101/2020.07.31.230243

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…Recently, a ferroptosis signature was reported in a case report of COVID-19 patient (48-year-old, male), showing 4-HNE, a reactive breakdown product of the lipid peroxides or oxidized phosphatidylcholine was positive in myocardial tissue staining and in the proximal tubules of acute kidney injury, with decreased lymphocytes in the blood 63 . An in vitro study also showed SARS-CoV-2 suppressed GPX4, the brake of ferroptosis 43 . These studies demonstrated the involvement of ferroptosis in SARS-CoV-2 infection and its potential contribution to the multiple organ damage.…”

Section: A Hypothesis On the Association Between Covid-19 And Ferroptmentioning

confidence: 92%

“…Iron is considered a critical player in COVID-19 pathogenesis 42 . A basic study used patient-derived SARS-CoV2 (SZ005) to infect African green monkey kidney (Vero) cells and found the expression of GPX4 was significantly decreased in mRNA levels, suggesting the association between SARS-CoV-2 and ferroptosis 43 . Owing to the lack of GPX4, GSH cannot be peroxidated to reduce lipid ROS generated from Fenton reaction.…”

Section: A Hypothesis On the Association Between Covid-19 And Ferroptmentioning

confidence: 99%

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SARS-CoV-2 infection: can ferroptosis be a potential treatment target for multiple organ involvement?

Yang

Lai

2020

Cell Death Discov.

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Since the outbreak of the new coronavirus in 2019 (SARS-CoV-2), many studies have been performed to better understand the basic mechanisms and clinical features of the disease. However, uncertainties of the underlying mechanisms of multiple organ involvement remain. A substantial proportion of severe coronavirus disease 2019 (COVID-19) patients have lymphopenia, low serum iron levels, and multiple organ involvement. Several therapeutic agents have been used for different stages of the disease, but the treatment for severe disease is still suboptimal. Understanding the mechanism of programmed cell death in COVID-19 may lead to better therapeutic strategies for these patients. On the basis of observations of basic science studies and clinical researches on COVID-19, we hypothesize that ferroptosis, a novel programmed cell death, may be an important cause of multiple organ involvement in COVID-19 and it might serve as a new treatment target. In spite of the existing findings on the involvement of ferroptosis in SARS-CoV-2 infection, there is no reported study to uncover how does ferroptosis acts in SARS-CoV-2 infection yet. Uncovering the role of ferroptosis in SARS-CoV-2 infection is essential to develop new treatment strategies for COVID-19. Intracellular cell iron depletion or new generation of ferroptosis inhibitors might be potential drug candidates for COVID-19. We hope this hypothesis may launch a new wave of studies to uncover the association of ferroptosis and SARS-CoV-2 infection in vitro and in vivo.

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Section: A Hypothesis On the Association Between Covid-19 And Ferroptmentioning

confidence: 92%

Section: A Hypothesis On the Association Between Covid-19 And Ferroptmentioning

confidence: 99%

SARS-CoV-2 infection: can ferroptosis be a potential treatment target for multiple organ involvement?

Yang

Lai

2020

Cell Death Discov.

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“…[5,6,7,8] SARS-CoV-2, like other RNA viruses, sequesters selenium causing selenium levels to drop during infection. [6,9] SARS-CoV-2 may infect cells in bone marrow, supressing red blood cell formation. [10] Selenium status is inversely associated with haemolysis in SCD, and may both inhibit haemolysis and enhance erythropoiesis in SCD.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Selenium supplementation may improve COVID-19 survival in sickle cell disease

Henderson

2021

Br J Nutr

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Sickle cell disease is associated with lower selenium levels, and the serum selenium level is inversely associated with haemolysis in SCD. The SCD population is more vulnerable to adverse COVID-19 outcomes. SARS-CoV-2 infection lowers the serum selenium level and this is associated with severity of COVID-19. Selenium supplementation is proposed to improve COVID-19 outcomes in the sickle cell disease population.

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“…Furthermore, selenium was observed to suppress the release of the inflammatory precursor cytokine that is activated by pathogens 12,13 . In cell studies, it was observed that cells infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) decreased selenoprotein synthesis and this decrease was found to be associated with the increase of IL‐6, an inflammatory marker 14 …”

Section: Introductionmentioning

confidence: 99%

“…12,13 In cell studies, it was observed that cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decreased selenoprotein synthesis and this decrease was found to be associated with the increase of IL-6, an inflammatory marker. 14 On the other hand, it was mentioned that selenium supplementation was beneficial for the regulation of immune response against thyroid autoimmunity during pregnancy and the post-partum period. 15 In an animal study, maternal selenium deficiency during pregnancy caused reduced fetal growth by reduced fetal glucose concentrations.…”

Section: Introductionmentioning

confidence: 99%

Maternal selenium status plays a crucial role on clinical outcomes of pregnant women with COVID‐19 infection

Erol

Polat

Akdas

et al. 2021

Journal of Medical Virology

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Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID‐19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID‐19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second ( p : .0003) and third ( p : .001) trimesters with COVID‐19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week ( p < .0001, r : −.541), D‐dimer ( p : .0002, r : −.363) and interleukin‐6 (IL‐6) level ( p : .02, r : −.243). In the second trimester, serum selenium level positively correlated with white blood cell ( p : .002, r : .424), neutrophil ( p : .006, r : .39), lymphocyte ( p : .004, r : .410) count and hemoglobin ( p : .02, r : .323), hematocrit ( p : .008, r : .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte ( p : .04, r : .353) and negatively correlated with C‐reactive protein level ( p : .03, r : −.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID‐19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL‐6 and D‐dimer levels, which indicate selenium's role in disease progression.

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SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, endoplasmic reticulum stress and DNA synthesis

Cited by 4 publications

References 26 publications

SARS-CoV-2 infection: can ferroptosis be a potential treatment target for multiple organ involvement?

SARS-CoV-2 infection: can ferroptosis be a potential treatment target for multiple organ involvement?

Selenium supplementation may improve COVID-19 survival in sickle cell disease

Maternal selenium status plays a crucial role on clinical outcomes of pregnant women with COVID‐19 infection

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