A rationale for targeting the P2X7 receptor in Coronavirus disease 19
Open accessAbstract
Severe pneumonia which shares several of the features of acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid‐19) for which there is no effective treatment, so far. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung oedema, inflammatory cell infiltration, and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid‐19‐associated severe pneumonia. Linked Articles: This article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
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Many processes associated with lung impairment, as seen in COVID-19 patients, are mediated by P2X7 receptors.
“As discussed by Di Virgilio et al. [106], many processes associated with lung impairment, as seen in COVID-19 patients, are mediated by P2X7 receptors [16].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [106]
P2X7 receptor activation may be involved in the cytokine storm observed in COVID-19 by stimulating NLRP3 inflammasome, overshooting inflammation with extensive cytokine release, affecting coagulation and leading to diffuse lung edema and infiltration by immune cells and inflammatory cytokines.
“Considering the P2X7 receptor role in inflammation, its activation may be involved in the cytokine storm observed in COVID-19 by stimulating NLRP3 inflammasome, overshooting inflammation with extensive cytokine release, affecting coagulation and leading to diffuse lung edema and infiltration by immune cells and inflammatory cytokines [106].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [106]
Pathological inflammation may be induced by P2X7 receptor activation, and its antagonism has been proposed as a therapeutic approach for COVID-19 treatment.
“Pathological inflammation may be induced by P2X7 receptor activation, and its antagonism has been proposed as a therapeutic approach for COVID-19 treatment [106].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [106]
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Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology
Ribeiro, D. E., Oliveira-Giacomelli, Á., Glaser, T., Arnaud-Sampaio, V. F., Andrejew, R., Dieckmann, L., Baranova, J., Lameu, C., Ratajczak, M. Z., & Ulrich, H. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00965-3 · Cited by 145 · see citing works
- Authors
- Di Virgilio, F., Tang, Y., Sarti, A. C., & Rossato, M.
- Affiliations
- Department of Medical Sciences University of Ferrara Ferrara Italy
- Chengdu University of Traditional Chinese Medicine (CN)
- University of Ferrara (IT)
- University of Padua (IT)
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2020-07-26
- Volume
- 177
- Issue
- 21
- Pages
- 4990-4994
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC7280564
- OpenAlex
- W3026471384
- Cited by
- 71
- References
- 40
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 7 · 2023: 10 · 2022: 20 · 2021: 19 · 2020: 11
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, other-oa)
- Funders
- UNIPDi
- Università degli Studi di Ferrara
- Associazione Italiana per la Ricerca sul Cancro (IG 13025, IG 18581, IG 22883)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- P2X7 receptor, COVID-19 pandemic, SARS-CoV-2, severe pneumonia, acute respiratory distress syndrome, cytokine storm, macrophage dysfunction, T cell dysfunction, pulmonary edema, inflammatory activation, therapeutic target
- MeSH terms
- Betacoronavirus, Cytokine Release Syndrome, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Animals, Humans, Macrophages, Pneumonia, Viral, Respiratory Distress Syndrome, T-Lymphocytes, Coronavirus Infections, Receptors, Purinergic P2X7, Pandemics
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