Nanoantibodies against coronavirus
Anti-coronavirus nano-antibodies were created from lam antibodies
British molecular biologists have used cells of the llama immune system to create miniature antibodies that can combine with a new type of coronavirus particles and prevent them from entering cells. The results of the first experiments with these antibodies were published by the scientific journal Nature Structural & Molecular Biology (Huo et al., Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2).
"The technology of growing nano-antibodies allows you to create molecules in almost real time that can very effectively neutralize new viral threats. We hope that H11-H4 and H11-D4 antibodies will become a component of drugs that will save the lives of severe patients or help form passive immunity," the researchers write.
Nano-antibodies are a special subtype of antibodies that consist of only one randomly arranged block, from which molecules of complete antibodies are usually assembled. Due to their size, nano-antibodies are more stable, so they better tolerate heat and aggressive chemical environments, including ingestion into the stomach and intestines.
Antibodies from heavy chains in sharks (left) and camels (center) in comparison with the usual antibody – immunoglobulin G (right). Heavy amino acid chains are colored dark, light – light.
Similar antibodies are not found in the human body and almost all other animals, but recently scientists have found them in blood samples and other biomaterials of camels, alpacas, llamas and sharks.
Recently, scientists from the USA and Belgium used immune cells of llamas to create universal multi-antibodies that can neutralize many strains of the influenza virus.
Molecular biologists, led by Professor James Naismith of Oxford University (UK), used lam immune cells to create two nano-antibodies at once, which can combine with the RBD protein, the main "fighting" part of the shell of a new type of coronavirus (SARS-CoV-2).
Nanoprotection against the virus
To do this, scientists prepared a random set of nano-antibodies with the help of lama cell cultures and tracked which of them would connect with fragments of the SARS-CoV-2 shell. Thanks to this, biologists isolated the H11 molecule, which was quite actively connected to the part of the protein envelope of the virus that is directly involved in the penetration into the cell.
Having discovered this nano-antibody, Naismith and his colleagues tried to improve it by introducing random mutations into a key part of its protein molecule that connected to the virus. After a while, biologists created two variations of the original antibody at once – H11-H4 and H11-D4. They were several hundred times stronger than him in terms of the effect on the virus.
Biologists have tested the work of these antibodies, as well as other molecules of this kind, on human cell cultures. These experiments showed that H11-H4 and H11-D4 significantly outperformed competitors in efficiency, completely blocking the virus in concentrations that were 3-5 times lower than those of other antibodies.
In addition, it turned out that the molecules block the wrong part of the RBD protein, which is attacked by other antibodies, including the VHH72 molecule, discovered by American biologists in experiments with lama cells in April this year. Due to this, they can be used in combination with each other, which will enhance the effect of such drugs and reduce the likelihood that the virus will become invulnerable to their action.
Such drugs, as scientists conclude, can be used not only for the treatment of severe forms of coronavirus, but also for the prevention of this disease. The fact is that if you inject H11-H4 and H11-D4 into the blood of healthy people, they will prevent the virus from entering human cells and start those processes that are associated with the development of coronavirus infection.
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