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Effects of Drugs Formerly Suggested for COVID-19 Repurposing on Pannexin1 Channels.
Caufriez, Anne; Tabernilla, Andrés; Van Campenhout, Raf; Cooreman, Axelle; Leroy, Kaat; Sanz Serrano, Julen; Kadam, Prashant; Dos Santos Rodrigues, Bruna; Lamouroux, Arthur; Ballet, Steven; Vinken, Mathieu.
  • Caufriez A; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Tabernilla A; Departments of Chemistry and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
  • Van Campenhout R; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Cooreman A; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Leroy K; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Sanz Serrano J; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Kadam P; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Dos Santos Rodrigues B; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Lamouroux A; Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
  • Ballet S; Departments of Chemistry and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
  • Vinken M; Departments of Chemistry and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Int J Mol Sci ; 23(10)2022 May 18.
Article in English | MEDLINE | ID: covidwho-1953481
ABSTRACT
Although many efforts have been made to elucidate the pathogenesis of COVID-19, the underlying mechanisms are yet to be fully uncovered. However, it is known that a dysfunctional immune response and the accompanying uncontrollable inflammation lead to troublesome outcomes in COVID-19 patients. Pannexin1 channels are put forward as interesting drug targets for the treatment of COVID-19 due to their key role in inflammation and their link to other viral infections. In the present study, we selected a panel of drugs previously tested in clinical trials as potential candidates for the treatment of COVID-19 early on in the pandemic, including hydroxychloroquine, chloroquine, azithromycin, dexamethasone, ribavirin, remdesivir, favipiravir, lopinavir, and ritonavir. The effect of the drugs on pannexin1 channels was assessed at a functional level by means of measurement of extracellular ATP release. Immunoblot analysis and real-time quantitative reversetranscription polymerase chain reaction analysis were used to study the potential of the drugs to alter pannexin1 protein and mRNA expression levels, respectively. Favipiravir, hydroxychloroquine, lopinavir, and the combination of lopinavir with ritonavir were found to inhibit pannexin1 channel activity without affecting pannexin1 protein or mRNA levels. Thusthree new inhibitors of pannexin1 channels were identified that, though currently not being used anymore for the treatment of COVID-19 patients, could be potential drug candidates for other pannexin1-related diseases.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Connexins / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23105664

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Connexins / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23105664