The research involved collaboration between Israeli and American researchers from the Hebrew University and the University of Pittsburgh, was recently published in the leading journal Nature Communications, and revealed amazing findings regarding the ability of nanoantibodies that come from animals to neutralize the corona virus, on its mutations. In addition, the research may help eradicate diseases similar to Corona in the future
A new international study conducted by research teams led by the American researcher Yi Shi from the University of Pittsburgh and Dr. Dina Schneidman from the School of Engineering and Computer Science at the Hebrew University, found nanoantibodies that neutralize the corona virus in animals - which are also very effective against mutations found in variants, including delta . The fascinating findings, announced a few days ago in the prestigious journal Nature Communications, describe three different mechanisms by which the nanoantibodies neutralize the virus, block it from infecting cells and prevent the onset of the disease. The structural analysis of the nanoantibodies performed by the researchers provides possibilities for the development of vaccines and future treatments that may act against a wide variety of corona viruses, including variants that have not yet appeared.
In a previous study by the pair of researchers and the research teams of each of them in their laboratories, Published in December of last year in the prestigious journal Science, reported for the first time the development of the technology to identify nanoantibodies using proteomics (the study of proteins in the body). The idea was developed before the spread of the corona epidemic around the world, and the researchers believed after the outbreak of the virus that the technology would be effective enough to lead to a scientific breakthrough. During my research of about three months, the researchers were able to quickly produce thousands of nanoantibodies to the spikes of the SARS-CoV-2 with specificity and ability to neutralize the virus at very high rates. Using computational structural modeling methods developed by Dr. Schneidman's group, the researchers mapped the exact location of each nanoantibody on the surface of the spikes of the corona virus, and this mapping revealed that nanoantibodies can use an abundance of new and advanced mechanisms to block virus infection.
Everything you wanted to know about the delta breed, but didn't feel comfortable asking
To produce the nanoantibodies, the researchers used a llama on an alpaca farm in Massachusetts. During their work, the researchers immunized a black female named Wally with a piece of spike protein from SARS-CoV-2 and after about two months her immune system produced nanoantibodies against the virus. The choice of Lemma was not accidental. All camels - camels, llamas, alpacas, vicunas and guanacos - produce antibodies similar to ours and alongside them smaller antibodies, whose molecular weight is about half that of a human antibody. These small antibodies are able to reach areas inaccessible to large antibodies like ours, and work more effectively. The complex task was to identify within the found nanoantibodies those with the best neutralizing ability to fight the corona virus. The precise structural mapping carried out by the researchers to nanoantibodies created in animals allowed the engineering of a new nanoantibody cocktail, which is able to cover the spikes of the corona in several places, thus preventing the virus from developing resistance to antibodies with the help of mutations. In collaboration with Prof. Paul Duprex, director of the Center for Vaccine Research in Pittsburgh, the researchers found that using a small fraction of a nanogram of the drug neutralizes viral particles sufficient to infect a million human cells. That is, their low dose is enough to neutralize the corona virus.
In the current study, which is a follow-up to the research in Science, which was led by student Tomer Cohen and Dina Schneidman from the Hebrew University, the researchers used tools they developed in the laboratory, based on deep learning, in order to model the new nanoantibodies. Today, the university laboratory is able to build 2D models of nanoantibodies with high precision and very quickly. Using their tools, the researchers concluded that some of the new nanoantibodies found against Corona bind to areas of the spike that do not undergo mutations and also to areas where normal antibodies have no access at all. The team selected eight structures of specific nanoantibodies from the tens of millions of nanoantibodies that were extracted from the llama for the preparation of the cocktail, and which were previously found to be very effective against the virus. Through observations, the researchers confirmed that several nanoantibodies also work against the alpha strain of the corona virus ("the British variant"), against the delta strain ("the Indian variant") and against other mutations of the SARS-CoV-XNUMX.
The researchers even tried to understand in depth how each structure of the nanoantibodies works, and as a result to plan sophisticated preventive actions. The researchers classified the nanoantibodies into three main groups, based on the way they interact with the spike proteins - the protrusions that surround the globular virus and act as "keys" to attack it. The first group of antibodies found competes with the part of the human cell to which the spike protein binds, preventing the virus from entering the cells. The second group of antibodies binds to a region in the spike protein that is preserved unchanged throughout several strains of the corona virus - including the original SARS-CoV. This means that nanoantibodies from this group may neutralize SARS-CoV-2 including its various variants, and even other corona viruses. Third-party nanoantibodies attach to a specific region of the spike protein that normal antibodies cannot access (due to their size and scope). By attaching to this region, the nanoantibody prevents the protein from folding in the way it needs to so it can enter human cells. "Finding these mechanisms is of enormous importance in preventing the virus from entering cells, not only for existing variants and those that may appear in the future, but also for other viruses from the corona family, which may develop into similar global diseases in the future," explains Tomer Cohen.
Unfortunately, it is not yet possible to use the nanoantibody cocktail, which has not yet fully passed the clinical trials stage. "The results of the research on the nanoantibodies continue to be promising, we are halfway there but we definitely see that there is hope on the horizon. Such approvals take time," says Dr. Schneidman this week. "If we can produce an innovative drug through the cocktail, it will be a treatment that can save lives - if given to patients in an early stage of the disease. In addition, anyone exposed to confirmed patients will be able to use this treatment also as a prophylactic (preventive) treatment."
More of the topic in Hayadan:
