In the blood of patients who recover in 2003, pneumonia caused by SARS-CoV, found antibodies capable of neutralizing SARS-CoV-2. They learn the S phase, the protein is conservative for both viruses, contact him and prevent to enter the cell. Scientists hope that the use of such antibodies in the treatment and prevention prevent the viruses to develop resistance that can emerge in the therapy of more oncospecific antibodies. Work published in the journal Nature.
For effective treatment with antibodies is important for them to choose the correct target, they will be contacted. It must be something important for virus site located on its surface. In the case of SARS-CoV-2, many researchers have concentrated on finding antibodies recognizing RBD-domain to its S-protein. He meets these requirements and is situated in relatively accessible to antibodies place and plays a key role in the contamination: if it is to protect the antibody, the virus can not latch on to human cells and will cease to be a threat.
While this choice is fraught with possible problems. It is known that for the length of this phase is different conservative: there are sequences that are unique to SARS-CoV-2, and more universal, which are similar within related groups of strains, which include SARS-CoV and SARS 2 Sam. Given the “love” of coronaviruses to recombination — the exchange of stretches of the genome between strains makes sense to look for antibodies recognizing conservative areas, so less chance of emergence of resistant mutant versions of the virus, and at the same time, these same antibodies may be useful in other coronavirus infections. Additionally, the use of RBD-domain as a target for antibodies is complicated by the fact that in some conformations of the S-protein can hide and make inaccessible to antibodies.
To find wide-spectrum antibodies Dora Pinto (Pinto Dora) and her colleagues from the Swiss company Humabs Biomed SA, was tested for efficacy against SARS-CoV-2 antibodies from the blood samples of the patient who recover from SARS in 2003. Of the 25 antibodies tested, eight were able to communicate with the S-protein of SARS-CoV-2 and one antibody (S309) are particularly promising. S309 has been able not only to communicate with the S-protein, but in addition neutralize SARS-CoV-2 and its secure counterpart (pseudovirus), which verify its ability to penetrate into cells.
With cryoelectron microscopy, researchers have discovered exactly how to communicate with each antibody and S-protein. It turned out that the antibody not associated with the RBD domain and the nearby stretch of 22 amino acids. This site turned out to be conservative among the isolates directly SARS-CoV-2 and other strains of coronaviruses of the same group, such as RaTG-13 and SARS-CoV. Previous research has shown that the complex of S-protein can be in the closed and open conformation, and S309 successfully associated with both options.
Judging from the 3D structure, the antibody does not compete directly with the receptor ACE2, closing him access to the RBD domain, so the mechanism by which this antibody neutralizes the virus, requires additional research. The researchers demonstrated that a well-S309 interacts with the Fc receptors of the cells of innate immunity and is able to activate them. To clearly neutralize the virus, the researchers propose to use them in the future antibodies in combination with other. By analogy with combinations of antibiotics such mixtures of antibodies should work better and will not allow you to escape and propagate mutant viruses that no longer recognized by any one antibody.
This is not the first antibodies to SARS, which proved to be potentially useful for new pandemic. Before that, we talked about a similar antibody 47D11, which found Dutch researchers.