Stem Cells Help Create COVID-19 Treatment

Cambridge scientists used embryonic stem cells to grow beating cardiomyocytes. Using this model, the researchers demonstrated how the heart is vulnerable to infection with SARS-CoV-2. This system successfully tested a new experimental peptide drug, DX600, preventing COVID-19 from entering heart cells.

Many organs in the human body suffer from a coronavirus infection. And the heart is no exception. SARS-CoV-2 attacks heart cells or cardiomyocytes, which contract and pump blood. It is believed that this may contribute to the onset of symptoms of long-term COVID-19.

Patients with heart disease are more than fourfold as likely to die from coronavirus, from 2.3% to 10.5%, compared to those with healthy hearts, according to a new study published in Communications Biology.

Infection occurs when SARS-CoV-2 enters cells using the angiotensin-converting enzyme 2 (ACE2). It binds through flexible outgrowths of the spike protein (S-protein) that make up the ‘corona’ of the virus. The spike protein and ACE2 are then cleaved, allowing the viral genetic material to enter the host cell. Further, the virus forces it to produce its copies instead of normal proteins – this is how the infection develops.

A group of scientists from the University of Cambridge used human embryonic stem cells (ESCs) to grow clusters of cardiomyocytes in the laboratory. When they contract, they mimic the behavior of cells in the body, as if they pumped blood in natural conditions. Importantly, these model heart cells also contain critical components needed to infect SARS-CoV-2, particularly the ACE2 receptor.

Working in special biosafety laboratories and using a safer modified synthetic (“pseudotyped”) virus carrying the SARS-CoV-2 spike protein, the team mimicked coronavirus infection of cardiomyocytes. Scientists then used this model to search for potential drugs to block the infection.

Dr. Sanjay Sinha from the Wellcome-MRC Cambridge Stem Cell Institute said:

«Using stem cells, we’ve managed to create a model which, in many ways, behaves just like a heart does, beating in rhythm. This has allowed us to look at how the coronavirus infects cells and, importantly, helps us screen possible drugs that might prevent damage to the heart».

The team showed that certain drugs targeting proteins involved in the entry of the SARS-CoV-2 virus significantly reduce infection rates. These include the experimental drug DX600 and ACE2 antibodies, which were previously shown to neutralize the pseudotyped SARS-CoV-2 virus.

DX600 is an ACE2 protein antagonist; that is, it acts explicitly on ACE2 and inhibits the activity of peptides that play a role in the penetration of the virus into the cell.

In this experiment, DX600 has been shown to be about seven times more effective in preventing infection than antibodies. However, the researchers say this may be due to its use at higher concentrations. The drug did not affect the number of cardiomyocytes, which characterizes its non-toxicity.

Professor Anthony Davenport from the Department of Medicine and a fellow at St Catharine’s College, Cambridge, said:

«The spike protein is like a key that fits into the ‘lock’ on the surface of the cells – the ACE2 receptor – allowing it entry. DX600 acts like gum, jamming the lock’s mechanism, making it much more difficult for the key to turn and unlock the cell door.

We need to do further research on this drug, but it could provide us with a new treatment to help reduce harm to the heart in patients recently infected with the virus, particularly those who already have underlying heart conditions or who have not been vaccinated. We believe it may also help reduce the symptoms of long COVID».