May 13, 2020
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A study on human monoclonal antibodies to coronavirus was reviewed

On March), we published news of the preprint of an article stating that scientists found human monoclonal antibodies to neutralize the new coronavirus. The study was conducted by scientists from the University of Utrecht (Universiteit Utrecht) in collaboration with the Medical Center of the University of Erasmus (Erasmus MC) and pharmaceutical company Harbor BioMed . It makes sense to treat studies at the preprint stage with a certain degree of caution, but this work went through a review filter and in early May was published in the journal Nature Communications . We will talk about it in more detail, as it gives hope for the development of a medicine.

Antibodies are proteins synthesized by plasma cells. They are part of the secondary immune response to the pathogen. Antibodies bind to the pathogen protein, the antigen, and thus can neutralize the harmful microbe. For some time now, scientists can mass-produce antibodies that are specifically tuned to interact with a specific antigen. In another way, these antibodies are called monoclonal, as they are produced by cells belonging to the same cell clone. Such antibodies can be produced in large quantities in laboratory conditions - it is enough to merge the B-cell and myeloma cell that produces the desired antibody to obtain a “hybridoma" - the antibody-producing cell that can multiply indefinitely. Monoclonal antibodies can be used for various purposes, for example, in the development of diagnostic tests or even for the treatment of patients. For example, there are drugs for the treatment of Ebola based on monoclonal antibodies.

Viruses SARS-CoV-2 causing COVID - 18, and SARS-CoV , the causative agent of SARS, belong to the subgenus Sarbekoviruses of the Coronavirus family. On the surface, they have spiky proteins that bind to the receptor ACE2 (angiotensin converting enzyme) of the cells of an infected person and thus ensure the penetration of the pathogen's genetic material into the cell. Spike proteins in SARS-CoV and SARS-CoV-2 are very similar in structure, 77, 5% of their amino acid sequence is the same. One way to neutralize the virus is to prevent the binding of tenon-like proteins to the receptor of ACE2 . And here can help monoclonal antibodies that potentially interfere with the binding of the spike protein and receptor ACE2 .

Так схематически изображают антитело. Букву Y образуют т.н. тяжёлые цепи, a кветвям Y прикреплены лёгкие цепи. Синим обозначен константный домен, ажёлтым— вариабельный домен, который как раз иподстраивается под тот или иной антиген.

This is a schematic representation of the antibody. The letter Y is formed by the so-called heavy chains, and light chains are attached to the Y branches. Blue indicates the constant domain, and yellow - the variable domain, which just adapts to a particular antigen.

The study was conducted as follows: first, in mice vaccinated against the pathogen H2L2 revealed 22 B-leukocyte.

H2L2 - transgenic mice specially "designed" so that their B-cells produce antibodies that have constant the heavy and light chain domains were as in mice, and the variable ones as in humans. For more details, click on the link ( in English. ).

Further, the hybridomas of these cells were obtained and propagated in bioreactors. Then the precipitate was weeded out, and 22 the antibody supernatant was checked by enzyme immunoassay ( ELISA), resulting in four types of cells producing antibodies that are effective against the new coronavirus. And one of these four types, 19 D , produced antibodies that are effective as against SARS-CoV , and against SARS-CoV-2 . Then a chimeric antibody 19 D 11 H2L2 was converted to completely human - on the constant domains of light and heavy chains of the IgG1 type, variable domains, like a chimeric antibody , were "hung" D H2L2 . Further, this antibody was sent for testing, in which it was shown that 22 D acted on both viruses and prevented penetration cell infection in cell culture Vero .

" 19 D 11 binds to a conserved epitope at the spike receptor binding site, and this explains its ability to simultaneously neutralize as SARS-CoV , and SARS-CoV-2 , ”comment the authors of the study.

Preserved Rowan (stored conservative) epitopes within each viral protein - a field with a minimum polimorfonoy activity and thus with strong epitope activity, allowing the same antibodies recognize different closely related viruses. Given the high frequency of virus mutations, it is beneficial to create antiviral vaccines aimed specifically at conserved epitopes of viral proteins.

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