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Cell Cultures and Organoids

Experimental Drug Blocks Growth of SARS-CoV-2 Coronavirus in Cell Cultures and Organoids

A trial drug called APN01 or human recombinant soluble ACE2 (hrsACE2) can significantly block early stages of SARS-CoV-2 infections, according to a paper published in the journal Cell.

In cell cultures analyzed in the study, APN01 inhibited the coronavirus load by a factor of 1,000-5,000. Image credit: Tibor Kulcsar / IMBA.

In cell cultures analyzed in the study, APN01 inhibited the coronavirus load by a factor of 1,000-5,000. Image credit: Tibor Kulcsar / IMBA.

“We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic,” said University of British Columbia’s Professor Josef Penninger, co-corresponding author of the paper.

ACE2, a protein on the surface of the cell membrane, is the key receptor for the spike glycoprotein of SARS-CoV-2.

In earlier work, Professor Penninger and colleagues identified ACE2 and found that in living organisms, ACE2 is the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003.

While the COVID-19 outbreak continues to spread around the globe, the absence of a clinically proven antiviral therapy or a treatment specifically targeting the critical SARS-CoV-2 receptor ACE2 on a molecular level has meant an empty arsenal for health care providers struggling to treat severe cases of COVID-19.

“Our new study provides very much needed direct evidence that APN01 soon to be tested in clinical trials by the European biotech company Apeiron Biologics, is useful as an antiviral therapy for COVID-19,” said Professor Arthur Slutsky, from the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital and the University of Toronto.

In cell cultures analyzed in the current study, APN01 inhibited the SARS-CoV-2 coronavirus load by a factor of 1,000-5,000.

In engineered replicas of human blood vessel and kidneys — organoids grown from human stem cells — the researchers demonstrated that SARS-CoV-2 can directly infect and duplicate itself in these tissues.

This provides important information on the development of the disease and the fact that severe cases of COVID-19 present with multi-organ failure and evidence of cardiovascular damage.

Clinical grade APN01 also reduced the SARS-CoV-2 infection in these engineered human tissues.

“Using organoids allows us to test in a very agile way treatments that are already being used for other diseases, or that are close to being validated. In these moments in which time is short, human organoids save the time that we would spend to test a new drug in the human setting,” said Professor Núria Montserrat, a researcher in the Institute for Bioengineering of Catalonia and co-corresponding author of the paper.

“The virus causing COVID-19 is a close sibling to the first SARS virus,” Professor Penninger said.

“Our previous work has helped to rapidly identify ACE2 as the entry gate for SARS-CoV-2, which explains a lot about the disease.”

“Now we know that a soluble form of ACE2 that catches the virus away, could be indeed a very rational therapy that specifically targets the gate the virus must take to infect us. There is hope for this horrible pandemic.”

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Vanessa Monteil et al. 2020. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell, in press; doi: 10.1016/j.cell.2020.04.004

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