Drug could block SARS-CoV-2 before it infects cells

As the Covid-19 epidemic continues to spread across the world, researchers from Karolinska Institute, in Stockholm (Sweden) and the University of British Columbia, in Vancouver (Canada), may have found a drug to prevent infection in the early stages of development of the disease. Their results were featured in the scientific journal Cell.

To carry out their work, the scientists used tissue samples from a patient with Covid-19. Objective: isolate and cultivate SARS-CoV-2, the virus causing the disease. Thus, they were able to show how the tip of the protein present in the virus binds to the cell receptor ACE2 (angiotensin converting enzyme 2) to enter human cells. This is the same mechanism used by the first SARS virus, which caused a major epidemic in 2002-2003.

A copy of an enzyme to decoy the virus and prevent it from infecting cells

By adding a genetically modified variant of the ACE2 protein, called hrsACE2 (for “human recombinant soluble ACE2”), the scientists sought to see if the virus could be stopped before it infects cells. Result: hrsACE2 reduces the viral growth of SARS-CoV-2 by a factor ranging from 1,000 to 5,000. A number that varies depending on the total quantity of the virus compared to that of hrsACE2.

“We think adding this copy of the enzyme, hrsACE2, attracts the virus to attach itself to the copy instead of the actual cells.explains Ali Mirazimi, assistant professor in the department of laboratory medicine at the Karolinska Institute, in a article published on the institution’s website. This distracts the virus from its goal of infecting cells to the same degree and should lead to a reduction in virus growth in the lungs and other organs..”

A clinical trial initiated

Although the study was limited to cell cultures and miniature organ reproduction, a phase II clinical trial has been initiated. Indeed, based on the results of the researchers, a drug called APN01 is currently being developed by the company Apeiron Biologics, in Vienna. It has just received regulatory authorizations for the treatment of 200 patients with Covid-19 in Austria, Germany and Denmark.

So far, only the early stages of infection have been studied

“The virus that causes Covid-19 is a close relative of the first SARSsays Josef Penninger, a professor at the University of British Columbia’s faculty of medicine. Our previous work helped quickly identify ACE2 receptors as an entry point for SARS-CoV-2, which explains a lot about the disease. We now know that a soluble form of ACE2 could indeed be a very rational treatment that specifically targets the door the virus has to take to infect us..”

One caveat, however: the current study only looked at the effect of the drug during the early stages of infection. According to the scientists, more research is needed to determine if it is also effective during advanced stages of disease development.

The virus could directly infect blood vessels and kidneys

While the ACE2 protein usually helps the lungs and other organs maintain normal function, it could damage cells when a virus binds to it. According to the researchers, this would explain why some patients with Covid-19 suffer from severe lung disease and multi-organ failure. Similarly, the team was able to show that the virus could directly infect blood vessels and kidneys, and multiply itself there.