Will sharks help in the fight against covid?
Shark antibodies – against the coronavirus family
Today, preventive vaccination is considered the most effective way to combat COVID-19. However, SARS-CoV-2 actively mutates, acquiring the ability to "escape" from vaccine antibodies, as well as from the natural immunity of those who have been ill. Over time, it becomes increasingly clear that to succeed in this fight, a variety of immune "weapons" may be required, including such exotic ones as analogues of shark proteins-"antibodies".
Among all the drugs from COVID-19, preparations of neutralizing human monoclonal antibodies directed against the surface S-protein of the SARS-CoV-2 virus stand out. Like our own antibodies that appeared in the body as a result of vaccination or disease, these "ready-made" antibodies block viral particles from entering cells. And in this sense, they can be not only a means of therapy, for example, for patients with weakened immunity, but also a kind of replacement for vaccination.
To date, several such human antibody preparations have already received permission from the American Food and Drug Administration (FDA) for emergency use in the treatment of COVID-19. An example is ronaprev (REGN-COV2), which is a "cocktail" of two neutralizing human monoclonal antibodies – casirivimab and imdevimab.
However, the appearance of such strains as omicron, with a large number of mutations, can seriously reduce the effectiveness of such therapy. It cannot be excluded that in the future there will be strains even more different from the current ones. In addition, other coronaviruses, which now infect only animals, can "jump over" to humans.
The solution to this problem may be found in a completely unexpected area. We are talking about the use of single-domain antibodies derived from shark antibodies to combat coronavirus.
Cartilaginous fish, which include sharks, are the most evolutionarily distant animals from mammals, in whose body antibodies are produced from heavy chains – IgNAR.
Not all antibodies can be used for treatment, but only the active part of this large molecule — the variable antigen binding domain (Variable New Antigen Receptor, VNAR). These tiny proteins are able to penetrate into such "gaps" and recognize structures that are inaccessible to human immunoglobulins (IgG).
Researchers from the USA and the UK have selected several candidate proteins from the huge molecular library of VNAR, which were tested for the ability to protect human cells from coronaviruses. Experiments have shown that, in general, all the selected proteins effectively neutralized both SARS-CoV-2 itself and some of its "relatives".
The most effective of them, VNAR 3B4, apparently blocks the process of attachment of the viral spike protein to the cell by binding to a certain "groove" in its structure. And since this molecular characteristic is typical for the surface proteins of different coronaviruses, VNAR 3B4 was able to effectively neutralize different viral variants. For example, the same MERS is a very dangerous virus of the Middle East respiratory syndrome, a rather distant relative of SARS. It may also be effective against omicron.
The second most effective protein, the "antibody", apparently blocks the spike protein using a different mechanism, but this candidate turned out to be more sensitive to mutations of its target. Probably the most effective against COVID-19 will be "cocktails" of several VNARS with different "abilities".
The researchers also made sure that VNAR proteins can neutralize the animal coronavirus WIV1-CoV. In nature, this virus has so far been detected only in bat populations, but in laboratory conditions it is able to infect human cells. And in this sense, the development of analogues of shark antibodies can become a kind of insurance for the future, because there is no guarantee that the situation with SARS-CoV-2 will not happen again, only with another coronavirus "hero".
Article by Ubah et al. Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography published in the journal Nature Communications.
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