Blood concentrations of proapoptotic sFas and antiapoptotic Bcl2 and COVID-19 patient mortality

Lorente, Leonardo; Martı́n, Marı́a; González-Rivero, Agustín F.; Pérez-Cejas, Antonia; Argüeso, Mónica; Pérez, A. González; Ramos-Gómez, Luis; Solé‐Violán, Jordi; Ramos, José Alberto Marcos y; Ojeda, Nazario; Jiménez, Alejandro

doi:10.1080/14737159.2021.1941880

Cited by 10 publications

(8 citation statements)

References 30 publications

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“…Lorente et al reported that soluble levels of sFas, a proapoptotic protein of the extrinsic pathway. were lower in patients who survived COVID-19 [38]. Interestingly, in line with our data, Cifaldi et al demonstrated that IL-6 directly reduced the expression of perforin and granzyme B [39].…”

Section: Discussionsupporting

confidence: 91%

NK and T Cell Immunological Signatures in Hospitalized Patients with COVID-19

Bergantini

d’Alessandro

Cameli

et al. 2021

Cells

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Severe acute respiratory syndrome caused by coronavirus 2 emerged in Wuhan (China) in December 2019 and has severely challenged the human population. NK and T cells are involved in the progression of COVID-19 infection through the ability of NK cells to modulate T-cell responses, and by the stimulation of cytokine release. No detailed investigation of the NK cell landscape in clinical SARS-CoV-2 infection has yet been reported. A total of 35 COVID-19 hospitalised patients were stratified for clinical severity and 17 healthy subjects were enrolled. NK cell subsets and T cell subsets were analysed with flow cytometry. Serum cytokines were detected with a bead-based multiplex assay. Fewer CD56dimCD16brightNKG2A+NK cells and a parallel increase in the CD56+CD69+NK, CD56+PD-1+NK, CD56+NKp44+NK subset were reported in COVID-19 than HC. A significantly higher adaptive/memory-like NK cell frequency in patients with severe disease than in those with mild and moderate phenotypes were reported. Moreover, adaptive/memory-like NK cell frequencies were significantly higher in patients who died than in survivors. Severe COVID-19 patients showed higher serum concentrations of IL-6 than mild and control groups. Direct correlation emerged for IL-6 and adaptive/memory-like NK. All these findings provide new insights into the immune response of patients with COVID-19. In particular, they demonstrate activation of NK through overexpression of CD69 and CD25 and show that PD-1 inhibitory signalling maintains an exhausted phenotype in NK cells. These results suggest that adaptive/memory-like NK cells could be the basis of promising targeted therapy for future viral infections.

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Section: Discussionsupporting

confidence: 91%

NK and T Cell Immunological Signatures in Hospitalized Patients with COVID-19

Bergantini

d’Alessandro

Cameli

et al. 2021

Cells

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“…However, the bioactive chemicals must be separated and purified to study the exact mechanism of action [29,30]. Furthermore, increasing soluble Fas and B-cell CLL/lymphoma-2 (Bcl2) levels in COVID-19 patients raises the fatality rate in COVID-19 individuals [31]. However, Colpomenia sinuosa (C. sinuosa)-treated HCT-116 cells have downregulated antiapoptotic Bcl 2, which leads to caspases activation [32].…”

Section: Introductionmentioning

confidence: 99%

In Silico Screening of Bioactive Compounds of Representative Seaweeds to Inhibit SARS-CoV-2 ACE2-Bound Omicron B.1.1.529 Spike Protein Trimer

et al. 2022

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Omicron is an emerging SARS-CoV-2 variant, evolved from the Indian delta variant B.1.617.2, which is currently infecting worldwide. The spike glycoprotein, an important molecule in the pathogenesis and transmissions of SARS-CoV-2 variants, especially omicron B.1.1.529, shows 37 mutations distributed over the trimeric protein domains. Notably, fifteen of these mutations reside in the receptor-binding domain of the spike glycoprotein, which may alter transmissibility and infectivity. Additionally, the omicron spike evades neutralization more efficiently than the delta spike. Most of the therapeutic antibodies are ineffective against the omicron variant, and double immunization with BioNTech-Pfizer (BNT162b2) might not adequately protect against severe disease induced by omicron B.1.1.529. So far, no efficient antiviral drugs are available against omicron. The present study identified the promising inhibitors from seaweed’s bioactive compounds to inhibit the omicron variant B.1.1.529. We have also compared the seaweed’s compounds with the standard drugs ceftriaxone and cefuroxime, which were suggested as beneficial antiviral drugs in COVID-19 treatment. Our molecular docking analysis revealed that caffeic acid hexoside (−6.4 kcal/mol; RMSD = 2.382 Å) and phloretin (−6.3 kcal/mol; RMSD = 0.061 Å) from Sargassum wightii (S. wightii) showed the inhibitory effect against the crucial residues ASN417, SER496, TYR501, and HIS505, which are supported for the inviolable omicron and angiotensin-converting enzyme II (ACE2) receptor interaction. Cholestan-3-ol, 2-methylene-, (3beta, 5 alpha) (CMBA) (−6.0 kcal/mol; RMSD = 3.074 Å) from Corallina officinalis (C. officinalis) manifested the strong inhibitory effect against the omicron RBD mutated residues LEU452 and ALA484, was magnificently observed as the essential residues in Indian delta variant B.1.617.2 previously. The standard drugs (ceftriaxone and cefuroxime) showed no or less inhibitory effect against RBD of omicron B.1.1.529. The present study also emphasized the pharmacological properties of the considered chemical compounds. The results could be used to develop potent seaweed-based antiviral drugs and/or dietary supplements to treat omicron B.1.1529-infected patients.

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“…The ROS mediated activation of MAPK pathway also suppresses the BCL2 expression in the cells (Changchien et al, 2015). The decreased levels of BCL2 were observed in COVID-19 mortality cases than in COVID-19 survivors (Lorente et al, 2021). On the other hand, withaferin A pretreatment has shown the reversal of BCL2 downregulation in bromobenzene induced mice models accompanied by decrease in the levels of inflammatory cytokines TNFα and IL1β along with the restoration of antioxidant enzymes levels that were suppressed by bromobenzene (Vedi & Sabina, 2016).…”

Section: Discussionmentioning

confidence: 96%

An in silico approach towards exploration of the oxidative stress resistance of major withanolides of Withania somnifera in relation to COVID-19 management

Vinodkumar

Santhanu

Natarajan

et al. 2021

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Oxidative stress is the state of imbalance between the production of reactive oxygen species (free radicals) in the biological system and the ability of the body to detoxify them resulting in increased accumulation of free radicals in the cells. This stress leads to weakening of the immune system thus leading to higher susceptibility to other infections as well. This also includes the weakening of the respiratory tract leading to increased susceptibility of viral infections as in the case of COVID-19. Treatment for any kind of abnormality requires the identification of the key target proteins and pathways that are being altered. Withania somnifera is being used in the traditional medicinal system to improve health and longevity thus creating a sense of mental as well as physical well being. The present study utilises network pharmacological approach to predict the potential oxidative stress targets of the three major withanolides: withanolide A, withaferin A and withanone. Primarily, the targets of the individual withanolides were obtained from the Swiss target and DIGEP-pred databases and the GO terms and lead hits related to oxidative stress were retrieved from AMIGO2 database. Totally 40 correlative hits were obtained as anti stress targets of the withanolides, which were subjected to functional enrichment and protein–protein interaction analysis to study the enriched pathways underlying oxidative stress response. Further the eleven crucial targets of the four selected pathways were analysed using molecular docking analysis. A total of forty protein hits were obtained as oxidative stress targets of the withanolides. Further, the pathway enrichment of these forty target genes showed the AGE RAGE signalling pathway as highly enriched pathway. Therefore, the AGE RAGE signalling pathway along with its underlying pathways namely MAPK signalling pathway, FOXO pathway and PI3-AKT pathway were chosen among all the other enriched pathways. Further the molecular docking analysis of the eleven target proteins falling under these four pathways showed good docking scores of the withanolides with all the eleven targets with the highest interaction against BCL2. From the above study, the biological targets and associated pathways of the withanolides have been retrieved. Thus the in silico approach undertaken in this study explores the role of the key withanolides in the antioxidant potential of the traditional medicinal plant Withania somnifera.

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Blood concentrations of proapoptotic sFas and antiapoptotic Bcl2 and COVID-19 patient mortality

Cited by 10 publications

References 30 publications

NK and T Cell Immunological Signatures in Hospitalized Patients with COVID-19

NK and T Cell Immunological Signatures in Hospitalized Patients with COVID-19

In Silico Screening of Bioactive Compounds of Representative Seaweeds to Inhibit SARS-CoV-2 ACE2-Bound Omicron B.1.1.529 Spike Protein Trimer

An in silico approach towards exploration of the oxidative stress resistance of major withanolides of Withania somnifera in relation to COVID-19 management

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