Refine
Year of publication
- 2021 (7) (remove)
Language
- English (7)
Has Fulltext
- yes (7)
Is part of the Bibliography
- no (7)
Keywords
- SARS-CoV-2 (3)
- COVID-19 (2)
- antiviral therapy (2)
- 2-deoxy-d-glucose (1)
- ACE inhibitor (1)
- AT1 receptor antagonist (1)
- CD47 (1)
- IAP (1)
- SIRPalpha (1)
- benfooxythiamine (1)
Institute
- Medizin (5)
- Frankfurt Institute for Advanced Studies (FIAS) (2)
- Informatik (2)
- Physik (2)
The production of K∗(892)0 and ϕ(1020) in pp collisions at s√ = 8 TeV was measured using Run 1 data collected by the ALICE collaboration at the LHC. The pT-differential yields d2N/dydpT in the range 0<pT<20 GeV/c for K∗0 and 0.4<pT<16 GeV/c for ϕ have been measured at midrapidity, |y|<0.5. Moreover, improved measurements of the K∗(892)0 and ϕ(1020) at s√=7TeV are presented. The collision energy dependence of pT distributions, pT-integrated yields and particle ratios in inelastic pp collisions are examined. The results are also compared with different collision systems. The values of the particle ratios are found to be similar to those measured at other LHC energies. In pp collisions a hardening of the particle spectra is observed with increasing energy, but at the same time it is also observed that the relative particle abundances are independent of the collision energy. The pT-differential yields of K∗0 and ϕ in pp collisions at s√=8 TeV are compared with the expectations of different Monte Carlo event generators.
The global polarization of the Λ and Λ¯¯¯¯ hyperons is measured for Pb-Pb collisions at sNN−−−√ = 2.76 and 5.02 TeV recorded with the ALICE at the LHC. The results are reported differentially as a function of collision centrality and hyperon's transverse momentum (pT) for the range of centrality 5-50%, 0.5<pT<5 GeV/c, and rapidity |y|<0.5. The hyperon global polarization averaged for Pb-Pb collisions at sNN−−−√ = 2.76 and 5.02 TeV is found to be consistent with zero, ⟨PH⟩ (%) ≈ - 0.01 ± 0.05 (stat.) ± 0.03 (syst.) in the collision centrality range 15-50%, where the largest signal is expected. The results are compatible with expectations based on an extrapolation from measurements at lower collision energies at RHIC, hydrodynamical model calculations, and empirical estimates based on collision energy dependence of directed flow, all of which predict the global polarization values at LHC energies of the order of 0.01%.
The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.
The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. Antiviral interventions are only effective prior to the onset of hyperinflammation. Hence, biomarkers are needed for the early identification and treatment of high-risk patients. Here, we show in a range of model systems and data from post mortem samples that SARS-CoV-2 infection results in increased levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells. Systematic literature searches also indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions which may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, CD47 is a candidate biomarker for severe COVID-19. Further research will have to show whether CD47 is a reliable diagnostic marker for the early identification of COVID-19 patients requiring antiviral therapy.
SARS-CoV-2 is causing the coronavirus disease 2019 (COVID-19) pandemic, for which effective pharmacological therapies are needed. SARS-CoV-2 induces a shift of the host cell metabolism towards glycolysis, and the glycolysis inhibitor 2-deoxy-d-glucose (2DG), which interferes with SARS-CoV-2 infection, is under development for the treatment of COVID-19 patients. The glycolytic pathway generates intermediates that supply the non-oxidative branch of the pentose phosphate pathway (PPP). In this study, the analysis of proteomics data indicated increased transketolase (TKT) levels in SARS-CoV-2-infected cells, suggesting that a role is played by the non-oxidative PPP. In agreement, the TKT inhibitor benfooxythiamine (BOT) inhibited SARS-CoV-2 replication and increased the anti-SARS-CoV-2 activity of 2DG. In conclusion, SARS-CoV-2 infection is associated with changes in the regulation of the PPP. The TKT inhibitor BOT inhibited SARS-CoV-2 replication and increased the activity of the glycolysis inhibitor 2DG. Notably, metabolic drugs like BOT and 2DG may also interfere with COVID-19-associated immunopathology by modifying the metabolism of immune cells in addition to inhibiting SARS-CoV-2 replication. Hence, they may improve COVID-19 therapy outcomes by exerting antiviral and immunomodulatory effects.
Blood-pressure-lowering drugs are proposed to foster SARS-CoV-2 infection by pharmacological upregulation of angiotensin-converting enzyme 2 (ACE2), the binding partner of the virus spike (S) protein, located on the surface of the host cells. Conversely, it is postulated that angiotensin–renin system antagonists may prevent lung damage caused by SARS-CoV-2 infection, by reducing angiotensin II levels, which can induce permeability of lung endothelial barrier via its interaction with the AT1 receptor (AT1R). Methods: We have investigated the influence of the ACE inhibitors (lisinopril, captopril) and the AT1 antagonists (telmisartan, olmesartan) on the level of ACE2 mRNA and protein expression as well as their influence on the cytopathic effect of SARS-CoV-2 and on the cell barrier integrity in a Caco-2 cell model. Results: The drugs revealed no effect on ACE2 mRNA and protein expression. ACE inhibitors and AT1R antagonist olmesartan did not influence the infection rate of SARS-CoV-2 and were unable to prevent the SARS-CoV-2-induced cell barrier disturbance. A concentration of 25 µg/mL telmisartan significantly reduced the virus replication rate. Conclusion: ACE inhibitors and AT1R antagonist showed neither beneficial nor detrimental effects on SARS-CoV-2-infection and cell barrier integrity in vitro at pharmacologically relevant concentrations.