CRISTINA SÁEZ – 03/04/2020
The researcher of ICREA Núria Montserrat, of the Institut de Bioenginyeria de Catalunya (IBEC), is a world reference in the development of kidney organelles in the laboratory. (IBEC)
Researchers from the Institut de Bioenginyeria de Catalunya (IBEC) together with an international team of scientists have identified a drug that blocks the SARS-CoV-2 virus in the early stages of infection. Using cell cultures and organelles, miniature replicas of real organs developed from human cells, have proven that this drug is able to reduce up to 5000 times the amount of virus present in the tissue.
These promising results, published in the journal Cell, have caused the biotechnological company that developed the drug, Apeiron Biologic, to announce yesterday that a clinical trial with 200 patients with advanced Covid-19 phases in Europe will begin imminently.
The drug, called APN01, already existed: it had been developed for the 2003 SARS epidemic, caused by a coronavirus very similar to the one behind the current Covid-19 pandemic, which as of April 3 has caused more than one million cases and killed more than 53,000 people worldwide. By 2003, APN01 had already been tested in a Phase I-II clinical trial to verify its toxicity and efficacy.
A clinical trial with 200 patients with advanced Covid-19 phases in Europe will begin imminently.
This drug does it to block the mechanism of the virus’s entry into human cells. This mechanism was discovered by researchers at British Columbia University (Canada), co-authors of this new work, who then found that the virus’s S protein (arranged on the surface and giving it the appearance of crown) binds to a human cell receptor called ACE2 (angiotensin-converting enzyme).
This receptor is not in all human cells, but is expressed in lung, heart, blood vessels, kidneys and intestine, which are precisely the tissues affected by Covid-19.
To check if in this new coronavirus, SARS-CoV-2, this was also the infection mechanism, the researchers used tissue samples from patients with Covid-19, from those who isolated and infected human cells in the laboratory and also, and that is where the group of researcher ICREA Núria Montserrat of IBEC, human kidney organelles, enters.
The fact that the ACE2 receptor is strongly expressed in the kidneys and that SARS-CoV-2 RNA can be found in the urine is what led researchers to use kidney organelles as a model.
“We had many questions about how the virus enters the cell, whether it used different mechanisms when infecting kidney, lung or heart cells. The organelles have allowed us to find out that the mechanism is the same and test a molecule in a human context, because they are human cells of the patients’ own infected tissue, but at a rate much higher than that of a trial with people”, explains to La Vanguardia Montserrat.
Thus, the researchers saw, that indeed, the S protein of the new coronavirus binds to the human cells that have this ACE2 receptor. “Our results shed light on how SARS-CoV-2 infects the body’s cells, including those of blood vessels and kidneys,” Ali Miramizi, a researcher at the Karolinska Institute, who has been studying coronaviruses and other pathogens such as Ebola for decades, says in a statement.
They then applied the drug to cell cultures and kidney organelles and saw that it was able to reduce viral load by 1000 to 5000 times, depending on the total amount of viruses and drugs used; also reduced viral replication.
The drug was able to reduce viral load between 1000 and 5000 times.
The drug has only been tested in the early stages of infection, because organelles can only be kept in cultivation for up to 15 days, but researchers are confident that the antiviral drug could also be effective in more advanced phases which, in fact, will try to test the trial that will begin in the coming weeks in Europe.
The next step will be, instead of infecting cell cultures and organelles with viruses isolated from a sample of patients, to work directly with samples of infected tissues. In this sense, IBEC collaborates with hospital Clínic de Barcelona and other Spanish centers to obtain these samples from Covid-19.
They will also use organelles to study what happens in people who are diabetic, have a worse prognosis, or in conditions of hypoxia or lack of oxygen, caused by more aggressive infections. “We will try to see if the drug works equal to equal doses. We could even try to connect the kidney, lung organelles to see the systemic effect,” says Montserrat.
Confocal microscopy image of a kidney organoid generated in vitro from human pluripotent stem cells that have been differentiated for 20 days using tridimendional cultures (IBEC)