UBC researchers claim find of COVID-19 trial drug

“There is hope for this horrible outbreak,” researcher says

University of British Columbia researchers say they have found a trial drug that blocks the cellular door the virus uses to infect people with COVID-19.

“There is hope for this horrible outbreak,” said UBC Life Sciences Institute director Dr. Josef Penninger.

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Penninger said the drug might soon be ready for testing.

He said a global team’s work provides new insights into the  SARS-CoV-2 virus and its interactions on a cellular level, as well as how the virus 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 outbreak,” he said.

Meanwhile, the World Health Organization (WHO) said March 20 that Thailand , Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain and Switzerland will be involved in a multi-country clinical study for potential treatments for COVID-19, part of a rapid global search for drugs to treat COVID-19.

Penninger’s team’s findings were published in the science journal Cell Friday.

Penninger said the finding holds some promise for a treatment capable of stopping early infection of the novel coronavirus that, as of April 4, has affected more than 1.16 million people and claimed the lives of 62,491people worldwide.

The study has involved researchers from Vancouver, Toronto, Spain and Sweden.

Penninger explained that cell membrane-surface protein ACE2 plays a key role in the outbreak.

In earlier work, Penninger and colleagues at the University of Toronto and the Institute of Molecular Biology in Vienna identified ACE2 as the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003.

What the new finding means, Penninger  said, is that “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 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 University of Toronto Dr. Art Slutsky, also a scientist at Toronto’s Keenan Research Centre for Biomedical Science at St. Michael’s Hospital.

What the researchers found through cell cultures is that the drug inhibited the coronavirus load. Using engineered replicas of human blood vessel and kidneys  – “organoids” grown from human stem cells – the researchers demonstrated the virus can directly infect and duplicate itself in such tissues.

What can be drawn from that, they said, is key information on the disease’s development and that severe cases of COVID-19 can lead to with multi-organ failure and cardiovascular damage.

“Clinical grade hrsACE2 also reduced the SARS-CoV-2 infection in these engineered human tissues,” they said.

 “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 Prof. Núria Montserrat of the Institute for Bioengineering in Catalonia, Spain.

“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,” Montserrat said.

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

“Now, we know that a soluble form of ACE2 could be indeed a very rational therapy that specifically targets the gate the virus must take to infect us.

The WHO team’s work, dubbed Solidarity, will test four different drugs or combinations – remdesivir, a combination of two drugs, lopinavir and ritonavir, the two drugs plus interferon beta, and chloroquine – and will compare their effectiveness to what is called standard of care – the regular support hospitals treating COVID-19 patients.

“This global problem requires urgent global solutions,” said WHO’s representative to Thailand, Daniel Kertesz. “The goal is to identify medicines that will save lives in the global battle to fight this virus.”

Research by Penninger’s team 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.

 

jhainsworth@glaciermedia.ca

@jhainswo

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