Effects of Drugs Formerly Proposed for COVID-19 Treatment on Connexin43 Hemichannels

Autor: Axelle Cooreman, Anne Caufriez, Andrés Tabernilla, Raf Van Campenhout, Kaat Leroy, Prashant Kadam, Julen Sanz Serrano, Bruna dos Santos Rodrigues, Pieter Annaert, Mathieu Vinken
Přispěvatelé: Pharmaceutical and Pharmacological Sciences, Experimental in vitro toxicology and dermato-cosmetology, Faculty of Medicine and Pharmacy
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 9; Pages: 5018
International Journal of Molecular Sciences
ISSN: 1422-0067
Popis: Connexin43 (Cx43) hemichannels form a pathway for cellular communication between the cell and its extracellular environment. Under pathological conditions, Cx43 hemichannels release adenosine triphosphate (ATP), which triggers inflammation. Over the past two years, azithromycin, chloroquine, dexamethasone, favipiravir, hydroxychloroquine, lopinavir, remdesivir, ribavirin, and ritonavir have been proposed as drugs for the treatment of the coronavirus disease 2019 (COVID-19), which is associated with prominent systemic inflammation. The current study aimed to investigate if Cx43 hemichannels, being key players in inflammation, could be affected by these drugs which were formerly designated as COVID-19 drugs. For this purpose, Cx43-transduced cells were exposed to these drugs. The effects on Cx43 hemichannel activity were assessed by measuring extracellular ATP release, while the effects at the transcriptional and translational levels were monitored by means of real-time quantitative reverse transcriptase polymerase chain reaction analysis and immunoblot analysis, respectively. Exposure to lopinavir and ritonavir combined (4:1 ratio), as well as to remdesivir, reduced Cx43 mRNA levels. None of the tested drugs affected Cx43 protein expression. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:23 issue:9 ispartof: location:Switzerland status: published
Databáze: OpenAIRE
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