Apoptosis induced by SARS-CoV-2: can we target it?

Donia, Ahmed; Bokhari, Habib

doi:10.1007/s10495-021-01656-2

Cited by 32 publications

(38 citation statements)

References 12 publications

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“…On the other hand, the negative effect in EPO expression may be exerted by the virus in an attempt to reduce the IFN-related [39,40] immune-modulatory function of erythropoietin [41]. Another reason for SARS-CoV-2 to target EPO could be the anti-apoptotic properties [42] of the encoded protein, as the virus induces cell death in VeroE6, shown in S8 Fig in S2 File [35] and also in previous studies [43,44]. To investigate the possibility that the virus-mediated effects on the expression of the genes under study in cell culture are related to hypoxia and/or cell viability, we analyzed their expression in airway epithelial cells under low oxygen tension as well as in a number of conditions that promote or not cell death.…”

Section: Sars-cov-2 Downregulates Ddc Dace2 and Epo In Cultured Cellsmentioning

confidence: 67%

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

et al. 2021

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L-Dopa decarboxylase (DDC) is the most significantly co-expressed gene with ACE2, which encodes for the SARS-CoV-2 receptor angiotensin-converting enzyme 2 and the interferon-inducible truncated isoform dACE2. Our group previously showed the importance of DDC in viral infections. We hereby aimed to investigate DDC expression in COVID-19 patients and cultured SARS-CoV-2-infected cells, also in association with ACE2 and dACE2. We concurrently evaluated the expression of the viral infection- and interferon-stimulated gene ISG56 and the immune-modulatory, hypoxia-regulated gene EPO. Viral load and mRNA levels of DDC, ACE2, dACE2, ISG56 and EPO were quantified by RT-qPCR in nasopharyngeal swab samples from COVID-19 patients, showing no or mild symptoms, and from non-infected individuals. Samples from influenza-infected patients were analyzed in comparison. SARS-CoV-2-mediated effects in host gene expression were validated in cultured virus-permissive epithelial cells. We found substantially higher gene expression of DDC in COVID-19 patients (7.6-fold; p = 1.2e-13) but not in influenza-infected ones, compared to non-infected subjects. dACE2 was more elevated (2.9-fold; p = 1.02e-16) than ACE2 (1.7-fold; p = 0.0005) in SARS-CoV-2-infected individuals. ISG56 (2.5-fold; p = 3.01e-6) and EPO (2.6-fold; p = 2.1e-13) were also increased. Detected differences were not attributed to enrichment of specific cell populations in nasopharyngeal tissue. While SARS-CoV-2 virus load was positively associated with ACE2 expression (r≥0.8, p<0.001), it negatively correlated with DDC, dACE2 (r≤−0.7, p<0.001) and EPO (r≤−0.5, p<0.05). Moreover, a statistically significant correlation between DDC and dACE2 expression was observed in nasopharyngeal swab and whole blood samples of both COVID-19 and non-infected individuals (r≥0.7). In VeroE6 cells, SARS-CoV-2 negatively affected DDC, ACE2, dACE2 and EPO mRNA levels, and induced cell death, while ISG56 was enhanced at early hours post-infection. Thus, the regulation of DDC, dACE2 and EPO expression in the SARS-CoV-2-infected nasopharyngeal tissue is possibly related with an orchestrated antiviral response of the infected host as the virus suppresses these genes to favor its propagation.

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Section: Sars-cov-2 Downregulates Ddc Dace2 and Epo In Cultured Cellsmentioning

confidence: 67%

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

et al. 2021

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“…The secreted TF evidently plays key role in initiating disseminated intravascular coagulation (DIC), a pathological state of systemic coagulation [ 161 ] that was evidently noted among SARS-CoV-2 infected patients [ 162 ]. Of note, targeted cell apoptosis remains to be the hallmark during SARS-CoV-2 infection and was shown to have a direct relationship with severity in COVID-19 patients [ 163 ]. Human macrophages, T lymphocytes and lung endothelial cells were shown to undergo apoptosis via caspase 8 activation by the SARS virus, where the externalizing phosphatidylserine (PS) from apoptotic cells are shown to possess pro-coagulant properties.…”

Section: Sars-cov-2 and Its Receptors In Blood Vessel Pathophysiologymentioning

confidence: 99%

The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

Veluswamy

Wacker

Stavridis

et al. 2021

Viruses

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The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.

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“…Apoptosis and RIG-I-like receptor signaling pathway were significantly enriched for module 2. This indicates that COVID 19 induces these important pathogenic pathways [48][49][50][51][52]. Apoptosis is a promising target for combating SARS-CoV-2 virus infection [48][49][50][51].…”

Section: Discussionmentioning

confidence: 97%

“…This indicates that COVID 19 induces these important pathogenic pathways [48][49][50][51][52]. Apoptosis is a promising target for combating SARS-CoV-2 virus infection [48][49][50][51].…”

Section: Discussionmentioning

confidence: 97%

Identifying potential novel insights for COVID-19 pathogenesis and therapeutics using an integrated bioinformatics analysis of host transcriptome

El-aarag

Mahmoud

ElHefnawi

2021

Preprint

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The molecular mechanisms underlying the pathogenesis of COVID-19 has not been fully discovered. This study aims to decipher potentially hidden parts of the pathogenesis of COVID-19, potential novel drug targets, and to identify potential drug candidates. Two gene expression profiles (GSE147507-GSE153970) were analyzed and overlapping differentially expressed genes (DEGs) were selected for which top enriched transcription factors and kinases were identified and pathway analysis was performed. Protein-protein interaction (PPI) of DEGs was constructed, hub genes were identified and module analysis was also performed. DGIdb database was used to identify drugs for the potential targets (hub genes and the most enriched transcription factors and kinases for DEGs). A drug-potential target network was constructed and drugs are ranked according to the degree. L1000FDW web-based utility was used to identify drugs that can reverse transcriptional profiles of COVID-19. We identified drugs currently in clinical trials and novel potential 8 drugs. Besides the well-known pathogenic pathways, It was found that axon guidance is a potential pathogenic pathway. Sema7A, which may exacerbate hypercytokinemia, is considered a potential novel drug target. Another potential novel pathway is related to TINF2 overexpression which may induce potential telomere dysfunction and hence DNA damage that may exacerbate lung fibrosis.

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Apoptosis induced by SARS-CoV-2: can we target it?

Cited by 32 publications

References 12 publications

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

Identifying potential novel insights for COVID-19 pathogenesis and therapeutics using an integrated bioinformatics analysis of host transcriptome

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