Authors: Lauren Woolfe, Future Science Group
A multi-institution team, led by Josef Penninger from the University of British Colombia (Vancouver, Canada) has demonstrated that a trial drug could inhibit the early stages of COVID-19 in engineered human tissue. This research was recently published in the journal Cell.
Angiotensin converting enzyme 2 (ACE2) was previously identified as a critical receptor for SARS-CoV entry into cells. More recently, the team also confirmed that the novel coronavirus strain SARS-CoV-2 relies on this receptor for cell invasion.
ACE2 is vital in the maintenance of organs and protects the lungs from injury. By binding via a spike protein, SARS-CoV-2 is endocytosed into the cell, allowing viral replication to begin. Utilizing this knowledge, the team sought to determine whether a human recombinant soluble ACE2 (hrsACE2), could reduce viral invasion and therefore, prevent respiratory distress.
“We believe adding this enzyme copy, hrsACE2, lures the virus to attach itself to the copy instead of the actual cells,” explained corresponding author Ali Mirazimi (Karolinska Institutet, Sweden). “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.”
The researchers isolated SARS-CoV-2 from a patient with COVID-19. The human tissue samples were processed, and through cell culture the team demonstrated that hrsACE2 inhibited viral load by a factor of 1000–5000.
There have been increasing reports that patients with COVID-19 experience multiple organ failure, as well as severe cardiovascular damage. By creating human organoids of blood vessels and kidneys, the researchers determined that the virus is able to invade other tissues, resulting in continued damage, and can also shed progeny virus. However, once given clinical-grade hrsACE2, SARS-CoV-2 infection was also significantly reduced and in combination these results suggest that hrsACE2 blocks the initial stages of COVID-19 in a dose-dependent manner.
“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,” stated Núria Montserrat (Institute for Bioengineering of Catalonia, Barcelona, Spain).
More research will be required to determine whether the drug is effective during later stages in the disease course. However, Apeiron Biologics (Vienna, Austria) is suggested to be currently planning a clinical pilot study on infected COVID-19 patients in China.
“We are hopeful our results have implications for the development of a novel drug for the treatment of this unprecedented pandemic” concluded Penninger.
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Sources: Monteli V, Kwon H, Prado P et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. doi:10.1016/j.cell.2020.04.004 (2020); https://news.ubc.ca/2020/04/02/ubc-led-study-finds-trial-drug-can-significantly-block-early-stages-of-covid-19-in-engineered-human-tissues/; https://news.ki.se/trial-drug-may-block-early-stages-of-covid-19-study-in-human-cells-shows?_ga=2.187751019.279970517.1585927824-1953935615.1585927824