UBC study offers insight into "key aspects" of what causes coronavirus

Apr 3 2020, 12:59 pm

An international team led by University of British Columbia (UBC) researcher Dr. Josef Penninger announced it has found a trial drug that effectively blocks the cellular door that the virus that causes COVID-19 uses to infect its hosts.

According to the research team, these findings hold promise as a treatment capable of stopping early infection of coronavirus, and provides new insights into key aspects of SARS-CoV-2, the virus that causes COVID-19, and its interactions on a cellular level, as well as how the virus can infect blood vessels and kidneys.

‘There is hope,” said Penninger.“We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic.”

This work, he furthered, stems from a 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.

“[The team has] been working tirelessly day and night for weeks to better understand the pathology of this disease and to provide breakthrough therapeutic options,” said Penninger.

ACE2 — a protein on the surface of the cell membrane — is now at centre 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 Vienna first 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. His laboratory also went on to link the protein to both cardiovascular disease and lung failure.

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 healthcare providers struggling to treat severe cases of COVID-19.

In cell cultures analyzed in the current study, hrsACE2 inhibited the 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 the virus can directly infect and duplicate itself in these tissues.

This, they said, 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 hrsACE2 also reduced the SARS-CoV-2 infection in these engineered human tissues.

“Our new study provides very much needed direct evidence that a drug — called 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 Dr. Art Slutsky, a scientist at the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital and professor at the University of Toronto, who is a collaborator on the study.

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

This research was supported in part by the Canadian federal government through emergency funding focused on accelerating the development, testing, and implementation of measures to deal with the COVID-19 outbreak.