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

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

International journal of molecular sciences (2022-05-15)
Axelle Cooreman, Anne Caufriez, Andrés Tabernilla, Raf Van Campenhout, Kaat Leroy, Prashant Kadam, Julen Sanz Serrano, Bruna Dos Santos Rodrigues, Pieter Annaert, Mathieu Vinken
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine, ≥98%
Sigma-Aldrich
Anti-Connexin-43 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Ritonavir, ≥98% (HPLC)
Sigma-Aldrich
Chloroquine diphosphate salt, powder or crystals, 98.5-101.0% (EP)
Sigma-Aldrich
Ribavirin, antiviral
Sigma-Aldrich
Adenosine 5′-triphosphate (ATP) Bioluminescent Assay Kit, for ATP quantitation
Sigma-Aldrich
Lopinavir, ≥98% (HPLC)