An international team of scientists led by investigator of the University of British Columbia (UBC, for its acronym in English), the doctor Josef Penninger, found a drug trial that effectively blocks the door cell that the SARS-CoV-2 used to infect their guests.
The findings, published today in the prestigious scientific journal Cell, are promising as a treatment able to halt the early infection of the novel coronavirus that has affected more than a million people and has claimed the lives of 50,000 around the world.
The study provides new knowledge on key aspects of the SARS-CoV-2, the virus that causes COVID-19, and their interactions at the cellular level, as well as on how the virus can infect the blood vessels and the kidneys.
“We hope that our results will have implications for the development of a new drug for the treatment of this unprecedented pandemic” says Penninger, professor of the faculty of medicine, UBC, director of the Institute of Life Sciences and the Chair of Research Canada 150 in Functional Genetic at UBC.
“This work comes from an amazing collaboration between academic researchers and companies, including the group’s gastrointestinal doctor Ryan Conder at Stemcell Technologies in Vancouver, Nuria Montserrat in Spain, the doctors Haibo Zhang and Art Slutsky from Toronto and especially the team of biology, infectious Ali Mirazimi in Sweden, who have been working tirelessly day and night for weeks to better understand the pathology of this disease and provide therapeutic options, innovative”.
ACE2, a protein on the surface of the cell membrane, it is now located in the center of the stage in this outbreak as the key receptor for the glycoprotein spike of SARS-CoV-2. In previous work, Penninger and his colleagues from the University of Toronto and the Institute of Molecular Biology, Vienna, identified for the first time, ACE2, and discovered that in living organisms, ACE2 is the key receptor for SARS, the viral respiratory disease recognized as a global threat in 2003. His laboratory also went on to link the protein with cardiovascular disease and pulmonary insufficiency.
Although the outbreak of COVID-19 continues to spread throughout the world, the absence of an antiviral therapy clinically proven or treatment directed specifically the critical receptor for SARS-CoV-2 ACE2 at the molecular level has meaning a arsenal gap for health care providers struggling to treat severe cases of COVID-19.
“Our new study provides direct evidence very necessary that a medication called APN01 (angiotensin-converting enzyme soluble recombinant human 2 – hrsACE2), which will soon be tested in clinical trials for the company’s european biotechnology Apeiron Biologics, it is useful as an antiviral therapy for COVID-19, ” says dr. Art Slutsky, a scientist at the Research Center Keenan for Biomedical Sciences Hospital St. Michael and professor at the University of Toronto, who collaborated on the study.
In cell cultures analyzed in the current study, hrsACE2 inhibited the burden of coronavirus by a factor of 1,000-5,000. In replicas designed of blood vessels, and kidneys human, organoid grown from human stem cells, the researchers showed that the virus can become infected directly and replicate in these tissues. This provides important information about the development of the disease and the fact that the severe cases of COVID-19 are presented with multi-organ failure and evidence of damage, cardiovascular damage. The clinical grade hrsACE2 also reduced the infection by SARS-CoV-2 in these human tissues designed.
“The use of organoids allows us to prove a very nimble treatments that are already in use for other diseases, or who are close to being validated. In these times when time is short, the organoids human save the time that dedicaríamos to test a new drug in the human environment “, explained Nuria Montserrat, a professor in the ICREA at the Institute of Bioengineering of Catalonia in Spain.
“The virus that causes COVID-19 is a brother close to the first SARS virus. Our previous work has helped to quickly identify ACE2 as the door of entry for the SARS-CoV-2, which explains a lot about the disease. We now know that a soluble form of ACE2 that traps the virus could actually be very rational therapy that is directed specifically to the door that the virus must take to infect us. There is hope for this horrible pandemic,” noted Penninger.
This research was supported in part by the canadian federal government through emergency funds focused on accelerating the development, testing and implementation of measures to address the outbreak of COVID-19.