IL-6: Relevance for immunopathology of SARS-CoV-2

Gubernatorova, Ekaterina O.; Горшкова, Е. А.; Polinova, Almina I.; Drutskaya, Marina S.

doi:10.1016/j.cytogfr.2020.05.009

Cited by 280 publications

(289 citation statements)

References 173 publications

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“…Notably, SARS-CoV-2 has not been found to enter red blood cells 42 . However, the possibility that BSG could act as an accessory binding receptor for the virus has been speculated in several publications to possibly explain in part the link between SARS-CoV-2 infection and hematological symptoms in patients 38,39,43,44 . Our data suggest this hypothesis should be treated cautiously.…”

Section: Discussionmentioning

confidence: 99%

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Shilts

Wright

2020

Preprint

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The spike protein of SARS-CoV-2 is known to enable viral invasion into human cells through direct binding to host receptors including ACE2. An alternate entry receptor for the virus was recently proposed to be basigin/CD147. These early studies have already prompted a clinical trial and multiple published hypotheses of the role of this host receptor in viral infection and pathogenesis. We sought to independently characterize the basigin-spike protein interaction. After conducting several lines of experiments, we report that we are unable to find evidence supporting the role of basigin as a putative spike-binding receptor. Recombinant forms of both the entire ectodomain and S1 domain of the SARS-CoV-2 spike protein that directly bind ACE2 do not interact with basigin expressed on the surface of human cells. Using specialized assays tailored to detect receptor interactions as weak or weaker than the proposed basigin-spike binding, we report no evidence for direct binding of the viral spike to either of the two common isoforms of basigin. Given the pressing need for clarity on which targets of SARS-CoV-2 may lead to promising therapeutics, we present these findings to allow more informed decisions about the translational relevance of this putative mechanism in the race to understand and treat COVID-19.

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Section: Discussionmentioning

confidence: 99%

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

Shilts

Wright

2020

Preprint

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“…A cytokine storm has been identified as hallmark of critical illness in COVID-19 patients; thus it is relevant that IL-6 levels were found to be positively correlated with disease severity. 7 When SARS-CoV-2 viral copy number in the cultured cells reached 4.4×10 9 ( Figure 1A), IL-6 was significantly up-regulated by 4.3-fold ( Figure 1B). It has been demonstrated that IL-6 can affect the selenoenzyme, glutathione peroxidase (GPX), in an isozyme-specific manner.…”

Section: Resultsmentioning

confidence: 98%

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

Wang

Huang

Sun

et al. 2020

Preprint

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A significant, positive association between selenium status and COVID-19 prognosis has recently been identified. The present study investigated the influence of SARS-CoV-2 on host selenoproteins which mediate many beneficial actions of selenium. We found that SARS-CoV-2 suppressed mRNA expression of selenoproteins associated with ferroptosis (GPX4), ER stress (SELENOF, SELENOK, SELENOM and SELENOS) and DNA synthesis (TXNRD3) in Vero cells, providing a deeper insight into the connection between selenium and SARS-CoV-2.

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“…On contrast, higher levels of tetrahydrobiopterin increase CD4 and CD8 responses [13]. It has also been described that acute inflammatory stimulation increases levels of plasma BH4, in parallel with increased IL-6 [14], which it has been widely associated with SARS-CoV-2 infection and severity [15, 16]. Recent articles where plasma samples from Covid-19 patients were analyzed by metabolomics have shown differences in metabolism caused by SARS-CoV-2 infection, especially in steroid, aminoacid and mitochondrial metabolism [17].…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations

Trilla-Fuertes¹,

Ramos-Ruíz

Blanca‐López

et al. 2020

Preprint

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Covid-19, caused by the SARS-CoV-2 virus, has reached the category of a worldwide pandemic. Even though intensive efforts, no effective treatments or a vaccine are available. Molecular characterization of the transcriptional response in Covid-19 patients could be helpful to identify therapeutic targets. In this study, RNAseq data from peripheral blood mononuclear cell samples from Covid-19 patients and healthy controls was analyzed from a functional point of view using probabilistic graphical models. Two networks were built: one based on genes differentially expressed between healthy and infected individuals and another one based on the 2,000 most variable genes in terms of expression in order to make a functional characterization. In the network based on differentially expressed genes, two inflammatory response nodes with different tendencies were identified, one related to cytokines and chemokines, and another one related to bacterial infections. In addition, differences in metabolism, which were studied in depth using Flux Balance Analysis, were identified. SARS-CoV2-infection caused alterations in glutamate, methionine and cysteine, and tetrahydrobiopterin metabolism. In the network based on 2,000 most variable genes, also two inflammatory nodes with different tendencies between healthy individuals and patients were identified. Similar to the other network, one was related to cytokines and chemokines. However, the other one, lower in Covid-19 patients, was related to allergic processes and self-regulation of the immune response. Also, we identified a decrease in T cell node activity and an increase in cell division node activity. In the current absence of treatments for these patients, functional characterization of the transcriptional response to SARS-CoV-2 infection could be helpful to define targetable processes. Therefore, these results may be relevant to propose new treatments.Author SummarySARS-CoV-2 infection caused Covid-19 which has reached the category of a worldwide pandemic. However, no treatments or vaccines are still available. For this reason, it is still necessary the molecular study of this disease. In this study, we reanalyzed data from peripheral blood mononuclear cells from Covid-19 patients and healthy controls using computational techniques that allow the study of differential biological processes and metabolic pathways. The results suggested a complex inflammatory response, involving genes related to response to bacterial infection and allergic processes, and alterations in metabolic pathways such as glutamate metabolism, cysteine and methionine metabolism or tetrahydrobiopterin metabolism. These processes could be used in the future as therapeutic targets in Covi-19 infection.

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IL-6: Relevance for immunopathology of SARS-CoV-2

Cited by 280 publications

References 173 publications

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

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

Functional characterization of SARS-CoV-2 infection suggests a complex inflammatory response and metabolic alterations

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