Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms23105664
Keywords
COVID-19; antiviral and anti-inflammatory drugs; pannexin1
Funding
- Research Foundation Flanders-Belgium
- Scientific Fund Willy Gepts-Belgium
- Methusalem program of the Flemish government
- European Union (ERC) [861913, 858014]
- European Research Council (ERC) [861913] Funding Source: European Research Council (ERC)
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Multiple drugs previously tested in clinical trials during the COVID-19 pandemic, including favipiravir, hydroxychloroquine, and lopinavir, were found to inhibit Pannexin1 channel activity without affecting protein or mRNA levels. Despite not currently being used for COVID-19 treatment, these drugs could serve as potential candidates for other Pannexin1-related diseases.
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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