SARS-CoV-2, the new coronavirus, gains entry into cells in the body using a receptor called angiotensin-converting enzyme 2 (ACE2).
ACE2 is present on the surface of cells in the airways and the lungs. After a person inhales viral particles, spike proteins on the outside of the virus bind to this receptor, which allows the virus to enter cells and cause disease.
Other coronaviruses, including the virus behind the 2002 SARS outbreak, also bind to the ACE2 receptor. However, it seems the new coronavirus binds to it more tightly, perhaps underlying its higher infectiousness.
Researchers from Tulane University in New Orleans, LA, have now developed an antibody that stops the virus from attaching to the ACE2 receptor, ultimately preventing infection.
In a paper on the preprint server bioRxiv, the researchers say that healthcare professionals could use the antibody both before and after a person has had exposure to SARS-CoV-2. It could be especially beneficial for people who cannot receive a vaccine for health reasons.
In an effort to trick the virus, the researchers behind the study designed a “decoy” ACE2, which the virus recognizes in the same way it does the real thing. However, it is not attached to cells in the body.
This decoy protein intercepts to neutralize the virus before it can attach to ACE2 on cells and cause infection.
Although scientists have used ACE2 in a soluble form before and it is safe in humans, it generally does not stay in the body for long and cannot reach the lining of the lungs — which is crucial for treating a respiratory virus.
To overcome these problems, the team attached ACE2 to the end of an antibody to increase its stability and transport in the body. They created four different antibodies, each with different mutations, to increase the ability of the drug to bind to the virus, its stability, and its half-life.
All of the antibodies worked against SARS-CoV-2, but one, called MDR504, was particularly effective. The virus bound more tightly to this particular antibody than it does to the natural ACE2 in the body.
This means that the antibody could effectively outcompete the ACE2 expressed on bodily cells, preventing the virus from infecting them.
In the next phase of their experiments, the researchers tested the drug in cells in culture using a pseudovirus very similar to SARS-CoV-2. They found that MDR504 effectively neutralized the virus and blocked it from entering the cells.
They next injected the antibody into mice, where it reached the lungs at levels likely high enough to stop the virus from entering the cells lining these organs.
“Unlike other agents in development against the virus, this protein is engineered to go to the lungs to neutralize the virus before it can infect lung cells.”
– Lead study author Dr. Jay Kolls, Tulane University
What is more, the antibody remained in the system for a long time. After 6 days, half of what the researchers injected was still in circulation in the mice.
The researchers also say that the antibody could be dual purpose; they could use it to prevent infection and as a treatment for COVID-19.
Initially, they suggest administering it to high risk groups, such as healthcare workers and first responders, to prevent them from contracting the novel coronavirus.
As the drug is an antibody, a doctor would need to inject it directly into the circulation rather than asking a person to take it orally. If they took it orally, the body would break it down in the gut.
However, because it also has a long half-life, these injections could be relatively infrequent, the researchers suggest.
“Based on our data, we think it would work as an injection either once every 2 weeks or maybe even once a month,” says Dr. Kolls.
Healthcare professionals could also use the drug in place of a vaccine (once one arrives) for those too vulnerable to receive one. This might include people receiving immunosuppressant treatment for an organ transplant or an autoimmune condition.
The team has already started collaborating with a biotechnology company to further develop the treatment and start the necessary clinical trials in humans.
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