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SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics

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dc.contributor.authorPrieto, Juan
dc.contributor.authorLucero, Claudia
dc.contributor.authorRovegno, Maximiliano
dc.contributor.authorGómez, Gonzalo
dc.contributor.authorRetamal, Mauricio A.
dc.contributor.authorOrellana, Juan
dc.date.accessioned2024-01-10T19:19:28Z
dc.date.available2024-01-10T19:19:28Z
dc.date.issued2023
dc.description.abstractBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels. Results: We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca2+]i dynamics elicited by ATP. Conclusions: We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.
dc.description.versionVersión Publicada
dc.identifier.citationPrieto-Villalobos J, Lucero CM, Rovegno M, Gómez GI, Retamal MA, Orellana JA. SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics. Biol Res. 2023 Oct 25;56(1):56. doi: 10.1186/s40659-023-00468-9
dc.identifier.doihttps://doi.org/10.1186/s40659-023-00468-9
dc.identifier.urihttps://repositorio.udd.cl/handle/11447/8326
dc.language.isoen
dc.subjectACE2
dc.subjectATP and spike S1
dc.subjectCOVID-19
dc.subjectConnexin 43
dc.subjectHemichannels
dc.subjectSARS-CoV-2
dc.titleSARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceBiological research
dspace.entity.typePublication
relation.isAuthorOfPublication01e4a6fa-e55f-47c5-a1b6-383d5fc6f474
relation.isAuthorOfPublication.latestForDiscovery01e4a6fa-e55f-47c5-a1b6-383d5fc6f474

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