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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.
DiNicolantonio, James J; Barroso-Aranda, Jorge.
  • DiNicolantonio JJ; Mid America Heart Institute, Kansas City, MO, USA. Electronic address: jjdinicol@gmail.com.
  • Barroso-Aranda J; Clinica Libre de Adicciones. Tijuana, B.C., Mexico.
Med Hypotheses ; 143: 110051, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-624899
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pentoxifylline / Pneumonia, Viral / Coronavirus Infections / Receptor, Adenosine A2A / Dipyridamole / Pandemics / Betacoronavirus Type of study: Experimental Studies / Observational study / Prognostic study Topics: Long Covid / Traditional medicine Limits: Animals / Humans Language: English Journal: Med Hypotheses Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pentoxifylline / Pneumonia, Viral / Coronavirus Infections / Receptor, Adenosine A2A / Dipyridamole / Pandemics / Betacoronavirus Type of study: Experimental Studies / Observational study / Prognostic study Topics: Long Covid / Traditional medicine Limits: Animals / Humans Language: English Journal: Med Hypotheses Year: 2020 Document Type: Article