We have previously reported that scientists have foundantibodies that can destroy any strain of coronavirus. In particular, recently such an antibody was discovered by Chinese scientists. This time, American scientists reported that they were able to identify an antibody that can treat a wide range of sarbecoviruses. SARS-CoV-2, which caused the COVID-19 pandemic, also belongs to this family of viruses. According to scientists, the antibody is effective against all currently existing strains of coronavirus. Laboratory studies conducted on animals have shown its high efficiency. Moreover, according to the authors of the work, the antibody prevents the virus from escaping it by mutation. So it is an excellent candidate for further clinical research and the creation of an effective drug against coronavirus.
Why the coronavirus eludes the immune system
Like other antibodies that are currentlybeing studied by scientists and likely to be used to treat coronavirus, S2K146 binds to a spike protein. Let me remind you that the spike protein, or S-protein of the virus, binds to the angiotensin-converting enzyme (ACE2) of a healthy cell. Simply put, it attaches to a specific area of the cell membrane for further penetration into the cell. Thus, the spike protein is responsible for the ability of the virus to infect cells and, accordingly, multiply in them.
Region of a spike protein that attaches toACE2 is called the receptor-binding domain. It is the main target of antibodies. By binding to it, antibodies block it, which means they do not allow the virus to enter the cell. It would seem that the key to the treatment of coronavirus lies on the surface, but not everything is so simple. SARS-CoV-2 mutates quite quickly, resulting in changes in the amino acid sequences of the receptor-binding domain of the spike protein. As a result of these mutations, antibodies no longer recognize this part of the virus, and for this reason they no longer attack it. Thus, the modified virus evades immunity.
In theory, mutations that allow you to escapeantibodies to the virus, disrupt its ability to attach to the cell membrane and infect the cell. But the spike protein of SARS-CoV-2, unlike many other viruses, has learned to mutate so that its ability to bind to ACE2 is preserved. That is why many antibodies, on the basis of which scientists planned to create drugs for coronavirus, turned out to be absolutely useless over time, while the virus itself spread across the planet with even greater force.
An antibody that remains effective against any mutation of the coronavirus
According to the authors of the work, which waspublished in the journal Science, generating a broad neutralizing sarbecovirus antibody response is key to fighting against SARS-CoV-2, as well as future similar viruses. It appears that the S2K146 antibody, which was derived from B cells, could provide such a response. It was found in a person who fell ill with COVID-19 and successfully recovered.
But how did the antibody prove to be effective,if the spike protein constantly mutates? The fact is that S2K146 has one important feature. The area that it uses as a target is almost identical to the area that recognizes the ACE2 receptor, that is, the most important element of the spike protein.
“S2K146 binds on the site thatattach to the cell. It mimics the molecular contacts that occur when it binds to the ACE2 receptor,” says David Wiesler, one of the authors of the work, at the Howard Hughes Medical Institute.
For this reason, any spike mutation thatprevents the antibody from finding the virus, while simultaneously reducing the ability of the virus to infect the cell. This assumption was confirmed experimentally. Scientists used a surrogate virus that has the SARS-CoV-2 spike protein and exposed it to S2K146. The purpose of the experiment was to find out whether mutations appear that allow eluding this antibody.
Subscribe to our Yandex.Zen channel, where you will find even more fascinating materials.
The team had to expose the virus to an antibody attackdozens of times. The result was only one variant that could elude S2K146, but its ability to bind to ACE2 was extremely low. As David Wiesler says, it is extremely unlikely that mutations will arise that can evade the antibody and still infect cells. However, this possibility still remains.
As for those variants of the virus that are noteluded the antibody, their ability to replicate was completely suppressed. In particular, during an experiment on rodents, S2K146 was able to completely suppress the ability of the virus to penetrate into lung cells. Finally, let me remind you that earlier scientists managed to find a vulnerability of the coronavirus, using which it is theoretically possible to block its ability to infect cells.