Beating heart cells grown in Cambridge lab demonstrate potential of Covid-19 experimental drug
Beating heart cells have been grown in the lab by University of Cambridge scientists, which have shown how they are vulnerable to infection by the Covid-19 virus.
They used the model to demonstrate how an experimental peptide drug called DX600 can prevent SARS-CoV-2 from entering the heart cells.
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 heart is one of the major organs damaged by SARS-CoV-2, which impacts cardiomyocytes - the heart cells that contract and circulate blood.
Damage to these cells may contribute to long Covid, scientists believe.
Case fatality rises fourfold in patients with underlying heart problems, from 2.3 per cent to 10.5 per cent.
The heart cells grown in the special biosafety lab contained the ACE2 receptor to which the virus’ spike protein binds. The researchers used a safer, modified synthetic ( or pseudotyped) virus with the spike protein to mimic how the virus enters the heart cells, before using the model to screen potential drugs that can block infection.
Some drugs targeting the proteins involved in SARS-CoV-2 viral entry significantly reduce infection levels, including an ACE2 antibody previously shown to neutralise pseudotyped SARS-CoV-2 virus.
The experimental DX600 proved seven times more effective than the antibody at preventing infection - although this may be because it was used in higher concentrations.
DX600 is described as an ACE2 peptide antagonist because it targets ACE2 and inhibits the activity of peptides that help the virus break into cells.
The drug did not affect the number of heart cells, suggesting it is unlikely to be toxic.
Prof 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.”
The research was largely supported by Wellcome, Addenbrooke’s Charitable Trust, Rosetrees Trust Charity and British Heart Foundation.
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