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Trial drug may block early COVID-19 infection

A new drug that will soon be tested in clinical trials may prevent early COVID-19 infection. An international team of experts has demonstrated the drug’s potential to block the cellular door used by SARS-CoV-2 to gain entry into human cells. 

SARS-CoV-2, or Severe Acute Respiratory Syndrome Coronavirus 2, is the scientific name of the virus that causes COVID-19. The virus shares close genetic ties with the first SARS coronavirus (SARS-CoV), which infiltrated 26 countries in 2003. 

Led by Dr. Josef Penninger of the University of British Columbia, the research is providing new insight into how SARS-CoV-2 behaves on a cellular level. “We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic,” said Dr. Penninger.

In previous research, Dr. Penninger and his colleagues determined that a protein found on the surface of human cells, angiotensin converting enzyme 2 (ACE2), serves as the key receptor for SARS. As the current COVID-19 pandemic persists, antiviral medications that can accurately target the ACE2 receptor are urgently needed.

“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 study co-author Dr. Art Slutsky of the University of Toronto.

Using organoids produced from human kidney and blood vessel stem cells, the experts showed that SARS-CoV-2 can infect these tissues directly and then duplicate itself after gaining entry. This discovery sheds new light on how the disease evolves. The finding also explains why some patients with severe cases of COVID-19 experience multi-organ failures and cardiovascular damage.

The study revealed that hrsACE2 effectively reduced SARS-CoV-2 infection in the organoids. In cell cultures, the researchers found that hrsACE2 inhibited the SARS-CoV-2 viral load by a factor of 1,000 to 5,000, depending on the dose.

“Our study provides new insights into how SARS-CoV-2 infects the cells of the body, including in blood vessels and kidneys,” said study co-author Ali Mirazimi. “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.”

Núria Montserrat, a professor at the Institute for Bioengineering of Catalonia in Spain, explained that the use of human organoids saves valuable time compared to testing new drugs on humans. 

“This work stems from an amazing collaboration among academic researchers and companies, including Dr. Ryan Conder’s gastrointestinal group at STEMCELL Technologies in Vancouver, Nuria Montserrat in Spain, Drs. Haibo Zhang and Art Slutsky from Toronto and especially Ali Mirazimi’s infectious biology team in Sweden, who have been working tirelessly day and night for weeks to better understand the pathology of this disease and to provide breakthrough therapeutic options,” said Dr. Penninger.

“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.”

The study is published in the journal Cell.

By Chrissy Sexton, Staff Writer


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