Scientists at the University of Göttingen in Germany have developed nanoищвшуы that effectively block the SARS-CoV-2 coronavirus and its new dangerous variants. At the same time, they are a thousand times superior to previously created analogs. Since nanoищвшуы can be produced at low cost and in large quantities, this new tool, in case of successful clinical trials, will be able to meet the global demand for therapeutic drugs against COVID-19. This is reported in an article published in The EMBO Journal.
Nanobodies are a smaller version of antibodies-molecules that attach to viruses and other infectious agents and neutralize them. Mini-antibodies, or VHH, are directed against the S-protein of the coronavirus, which is involved in attaching the virus to receptors on the surface of the infected cell and then penetrating it inside. Nanobodies block the receptor-binding domain of the coronavirus, preventing infection.
To create the nanobodies, the scientists immunized three alpacas to produce mini-antibodies to the S-protein. The researchers then took blood samples and isolated about a billion different antibodies. To select the 45 most effective molecules, bacteriophages were used that carried a receptor-binding domain of the coronavirus on their surface. After that, the nanobodies were tested for the effectiveness of neutralizing SARS-CoV-2 and preventing the replication of the virus in cells.
The researchers also constructed various structures from nanobodies. For example, triads consisting of several molecules — three identical nanobodies connected. The triad corresponds to the symmetry of the three receptor-binding domains of the S-protein, which cannot be released, which increases the efficiency of neutralizing the virus by 30 thousand times compared to single bodies. In addition, in this case, the release of nanobodies from the body slows down, contributing to a longer therapeutic effect.
Tandems — bundles of two molecules-have become another option for using nanobodies. They target different parts of the receptor-binding domain and together block the S-protein. It is proved that single, double, and triple nanobodies can stop the pathogen even in tiny quantities.