Friday, April 3, 2020
Trial drug can significantly block early stages of COVID-19 in engineered human tissues
April 2, 2020:University of British Columbia:An international team has found a trial drug that effectively blocks the cellular door SARS-CoV-2 uses to infect its hosts.
https://www.sciencedaily.com/releases/2020/04/200402144526.htm
An international team led by University of British Columbia researcher Dr. Josef Penninger has found a trial drug that effectively blocks the cellular door SARS-CoV-2 uses to infect its hosts.
The findings, published today in Cell, hold promise as a treatment capable of stopping early infection of the novel coronavirus that, as of April 2, has affected more than 981,000 people and claimed the lives of 50,000 people worldwide.
The study 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.
"We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic," says Penninger, professor in UBC's faculty of medicine, director of the Life Sciences Institute and the Canada 150 Research Chair in Functional Genetics at UBC.
"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."
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 health care providers struggling to treat severe cases of COVID-19.
"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," says 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.
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 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.
"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," says Núria Montserrat, ICREA professor at the Institute for Bioengineering of Catalonia in Spain.
"The virus causing COVID-19 is a close sibling to the first SARS virus," adds 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."
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.
Story Source:
Materials provided by University of British Columbia. Note: Content may be edited for style and length.
Journal Reference:
Vanessa Monteil, Hyesoo Kwon, Patricia Prado, Astrid Hagelkrüys, Reiner A. Wimmer, Martin Stahl, Alexandra Leopoldi, Elena Garreta, Carmen Hurtado Del Pozo, Felipe Prosper, J.p. Romero, Gerald Wirnsberger, Haibo Zhang, Arthur S. Slutsky, Ryan Conder, Nuria Montserrat, Ali Mirazimi, Josef M. Penninger. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Submitted to Cell, 2020 DOI: 10.1016/j.cell.2020.04.004
Message from Democratic Socialists of America
In the wealthiest country in the history of the world, private health insurance and pharma companies have left us unforgivably vulnerable to the pandemic and hospitals now compete for ventilators on the free market, leading to a price jump from $20,000 to $40,000 each in just two weeks. Forty years of neoliberal austerity budgets are culminating, in the case of my own state of New York, in 2.5 billion dollars in Medicaid cuts by Democratic Governor Andrew Cuomo in our state budget. He’s also taking the opportunity to roll back historic bail law reforms which our movement had only just won months ago. Every state has its own story.
Wall Street Democrats have warned us for months that “if you like your health insurance now, you can keep it” to scare us away from Medicare for All. Now that the politicians have allowed 40 million people to lose work, and those of us still with private insurance face a 40% premium costs hike in 2021, a whole lot are realizing that was a hollow promise. Meanwhile, Donald Trump seeks to expand his right to detain us without trial, a power grab reminiscent of that completed by Hungary’s Viktor Orban just days ago, and deflects our fear and anger towards China and Chinese people.
We think we are at the mercy of the capitalist class.
But now is the time to think differently. As we huddle at home wondering where to get next month’s rent or tomorrow's meal or whether ICE will come knocking, or venture into danger to make low wages doing essential work, or grieve in solitude the losses of friends, family or coworkers, it is the time to recognize our place. Our place is not at the bottom of the economic pyramid. It is not gasping for breath because a wealthy politician decided we are expendable.
In truth, our place is running this economy, and controlling it too.
Workers walked off the job at multiple Amazon worksites here and abroad, this week at Instacart & Whole Foods, and last week it was nurses, sanitation workers, meatpackers and others. Hazard pay, paid sick leave and personal protective equipment are becoming common demands as essential workers realize they are indeed essential. And they are often winning.
But the thing that gives me the most hope, besides people realizing our collective power to protect ourselves and each other, is what I heard about General Electric workers: they demanded to make ventilators.
In the face of a deadly White House and often complicit Democratic politicians, workers are looking out for each other, demanding to control the means of production so they can meet human needs not corporate profits.
I am a socialist because I know that even after the tidal wave of layoffs in March, if we stand together we have the power not just to survive. We have the power to transform this society. We can change the capitalist economy that set us up to fail when the virus hit, and instead build a democratic socialist one. We can make an economy and society for the benefit of the many, not the few.
Our April Dispatch is full of ways you can get involved even while physically distant as well as organizing co-workers or neighbors if you have no choice but to go out.
We are in this together.
Maria Svart
DSA National Director
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