SARS-CoV-2 spike protein S1 activates Cx43 hemichannels

There are probably no people in the world nowadays who haven’t heard about the COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, an abbreviation for “Severe Acute Respiratory Syndrome Coronavirus 2.” This global pandemic, which began in 2019, has claimed millions of lives and disrupted the socio-economic fabric of societies worldwide.

The capacity of SARS-CoV-2 to infect humans lies in its structural components, particularly the spike protein that facilitates its entry into host cells. Therefore, it’s not surprising that this spike protein has attracted increased attention from scientists and is the target for many of the vaccines and therapeutic strategies currently in use.

It has been previously proposed that the acute and long-lasting symptoms of COVID-19 patients may originate from the direct action of the spike protein, but the mechanisms by which this viral protein could disturb cellular function remain to be fully elucidated.

In a recent study, scientists from the Pontifical Catholic University of Chile found out that the SARS-CoV-2 spike protein S1 increases the activity of Cx43 hemichannels in a time- and dose-dependent manner. The authors utilized an automated patch clamp system, the Patchliner, to reveal that the spike protein increases Cx43-mediated currents. Importantly, the responses to the spike protein were potentiated when the angiotensin-converting enzyme 2 (ACE2) was present in the cells.

Interestingly, the study provides evidence that the activation of Cx43 hemichannels by the SARS-CoV-2 spike protein S1 could lead to the release of ATP, disturbing intracellular calcium homeostasis. This suggests that the spike protein S1 could directly contribute to tissue dysfunction and damage seen in COVID-19 cases, including long-COVID symptoms. These findings could also potentially explain some of the adverse effects seen with SARS-CoV-2 vaccines.

In conclusion, this study suggests a novel mechanism through which SARS-CoV-2 disrupts cell function and positions Cx43 hemichannels as potential pharmacological targets for developing therapies to counteract the infection by SARS-CoV-2 and the long-term consequences of COVID-19.

Find the full article here.

Read more about ion channels and transporters involved in respiratory diseases here.

Learn more about the uses of automated patch-clamp systems for your research here.