- Sep 23, 2021
Scientists have found a trial drug that effectively blocks the cellular door SARS-CoV-2 uses to infect its hosts, an advance that they say may provide a potential treatment for the novel coronavirus.
The study, published in the journal Cell, provides new insights into key aspects of SARS-CoV-2, the virus that causes COVID-19.
It also provides details about the interactions of the virus on a cellular level, as well as how it can infect blood vessels and kidneys.
“We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic,” said Josef Penninger, from the University of British Columbia in Canada.
The researchers said ACE2 — a protein on the surface of the cell membrane — is now at center-stage in this outbreak as the key receptor for the spike glycoprotein of SARS-CoV-2.
In earlier work, Penninger and colleagues at the University of Toronto and the Institute of Molecular Biology in Austria found that in living organisms, ACE2 is the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003.
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, the researchers said.
“Our new study provides very much needed direct evidence that a drug — called APN01 (human recombinant soluble angiotensin-converting enzyme 2 — hrsACE2) — soon to be tested in clinical trials by the European biotech company Apeiron Biologics, is useful as an antiviral therapy for COVID-19,” said Art Slutsky, a professor at the University of Toronto.
In cell cultures, hrsACE2 inhibited the coronavirus load by a factor of 1,000-5,000, the researchers found. In engineered replicas of human blood vessel and kidneys — organoids grown from human stem cells — the researchers demonstrated that the virus 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, they said.
The team found that clinical grade hrsACE2 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,” said Nuria Montserrat, a professor at the Institute for Bioengineering of Catalonia in Spain.
“The virus causing COVID-19 is a close sibling to the first SARS virus,” Penninger added.
Previous work helped the researchers to rapidly identify ACE2 as the entry gate for SARS-CoV-2, which explains a lot about the disease.
In the latest study, they found that a soluble form of ACE2 that catches the virus away could be a very rational therapy that specifically targets the gate the virus must take to infect people.