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10.1016/j.mehy.2020.110051

http://scihub22266oqcxt.onion/10.1016/j.mehy.2020.110051
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suck abstract from ncbi


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pmid32650197      Med+Hypotheses 2020 ; 143 (ä): 110051
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  • Harnessing adenosine A2A receptors as a strategy for suppressing the lung inflammation and thrombotic complications of COVID-19: Potential of pentoxifylline and dipyridamole #MMPMID32650197
  • DiNicolantonio JJ; Barroso-Aranda J
  • Med Hypotheses 2020[Oct]; 143 (ä): 110051 PMID32650197show ga
  • Counterproductive lung inflammation and dysregulated thrombosis contribute importantly to the lethality of advanced COVID-19. Adenosine A2A receptors (A2AR), expressed by a wide range of immune cells, as well as endothelial cells and platelets, exert cAMP-mediated anti-inflammatory and anti-thrombotic effects that potentially could be highly protective in this regard. The venerable drug pentoxifylline (PTX) exerts both anti-inflammatory and antithrombotic effects that reflect its ability to boost the responsiveness of A2AR to extracellular adenosine. The platelet-stabilizing drug dipyridamole (DIP) blocks intracellular uptake of extracellularly-generated adenosine, thereby up-regulating A2AR signaling in a way that should be functionally complementary to the impact of PTX in that regard. Moreover, DIP has recently been reported to slow the cellular replication of SARS-CoV-2 in clinically feasible concentrations. Both PTX and DIP are reasonably safe, well-tolerated, widely available, and inexpensive drugs. When COVID-19 patients can be treated within several days of symptom onset, using PTX + DIP in conjunction with hydroxychloroquine (HCQ) and an antibiotic - azithromycin (AZM) or doxycycline - might be warranted. HCQ and AZM can suppress SARS-CoV-2 proliferation in vitro and may slow the cell-to-cell spread of the virus; a large case series evaluating this combination in early-stage patients reported an impressively low mortality rate. However, whereas HCQ and AZM can promote QT interval lengthening and may be contraindicated in more advanced COVID-19 entailing cardiac damage, doxycycline has no such effect and exerts a potentially beneficial anti-inflammatory action. In contrast to HCQ, we propose that the combination of PTX + DIP can be used in both early and advanced stages of COVID-19. Concurrent use of certain nutraceuticals - yeast beta-glucan, zinc, vitamin D, spirulina, phase 2 inducers, N-acetylcysteine, glucosamine, quercetin, and magnesium - might also improve therapeutic outcomes in COVID-19.
  • |*Betacoronavirus/drug effects/immunology/physiology[MESH]
  • |*Pandemics[MESH]
  • |Adenosine A2 Receptor Agonists/therapeutic use[MESH]
  • |Animals[MESH]
  • |Anti-Inflammatory Agents, Non-Steroidal/therapeutic use[MESH]
  • |COVID-19[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |Coronavirus Infections/complications/*drug therapy/metabolism[MESH]
  • |Dietary Supplements[MESH]
  • |Dipyridamole/*therapeutic use[MESH]
  • |Fibrinolytic Agents/therapeutic use[MESH]
  • |Humans[MESH]
  • |Models, Biological[MESH]
  • |Pentoxifylline/*therapeutic use[MESH]
  • |Pneumonia, Viral/complications/*drug therapy/metabolism[MESH]
  • |Pneumonia/etiology/prevention & control[MESH]
  • |Receptor, Adenosine A2A/*metabolism[MESH]
  • |SARS-CoV-2[MESH]
  • |Signal Transduction/drug effects[MESH]
  • |Thrombosis/etiology/prevention & control[MESH]
  • |Translational Research, Biomedical[MESH]


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