Decoy ACE2 receptors could be promising COVID-19 infection-preventing drug

Collaborative research has revealed a drug candidate that could inhibit the SARS-CoV-2 virus causing the COVID-19 pandemic infecting cells through Spike (S) proteins binding to the human angiotensin converting enzyme (ACE2).

Using cell cultures and organoids, researchers from the Karolinska Institutet in Sweden and the University of British Columbia (UBC) in Canada, showed that by adding a genetically modified variant of ACE2, called human recombinant soluble angiotensin-converting enzyme 2 (hrsACE2), COVID-19 was prevented from entering cells.

The paper, published in Cell, shows that hrsACE2 had a dose dependent effect of viral growth of SARS-CoV-2 and was able to reduce it by a factor of 1,000 to 5,000 in cell cultures.

The researchers also used blood vessel and kidney organoids to demonstrate that SARS-CoV-2 can directly infect and multiply within these tissues, a possible cause of the multi-organ failures and cardiovascular damage seen in severe COVID-19 cases. The addition of hrsACE2 also reduced the SARS-CoV-2 infection in these organoids.

In cell cultures analysed in the current study, hrsACE2 inhibited the coronavirus load by a factor of 1,000-5,000 [credit: IMBA/Tibor Kulcsar].

“Our study provides new insights into how SARS-CoV-2 infects the cells of the body, including in blood vessels and kidneys,” said Ali Mirazimi, adjunct professor at the Department of Laboratory Medicine at Karolinska Institutet and one of the study’s corresponding authors. “We believe adding this enzyme copy, hrsACE2, lures the virus to attach itself to the copy instead of the actual cells… It distracts the virus from infecting the cells to the same degree and should lead to a reduction in the growth of the virus in the lungs and other organs.”

While the research has so far been limited to cell cultures and organoids, Aperion Biologics has announced it plans to conduct a clinical pilot study on infected COVID-19 patients in China with its drug APN001, which contains hrsACE2 as an active substance. APN001 was designed and has been tested in Phase II trials for lung disease.

The researchers highlighted that their experiments have only examined the drug’s effect during the initial stages of SARS-CoV-2 infection and that further research is needed to determine if it is also effective during later stages of disease development.