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Among the tests to find an effective drug against COVID-19, many researchers have bet that the answer may lie in the blood of those patients who have already been infected with the new coronavirus (SARS-CoV-2) and have recovered. To investigate the issue, scientists at the Butantan Institute in São Paulo are working on the development of a compound with antibodies from survivors.
The concept behind the initiative is that each antigen (in this case, the coronavirus) leads to the production of a certain antibody in the blood of the infected person and it is this antibody that allows him or her to survive the disease. Furthermore, each antibody only acts on a single antigen, so if scientists discover which antibody is related to COVID-19 or when they discover it, they most likely have an effective defense against this infection.
In the Butantan study, neutralizing monoclonal antibodies, as they are called, will be selected from defense cells, lymphocytes, from which they have been cured of COVID-19. In this way, research looks for one or more of these proteins with the ability to bind the virus efficiently enough to neutralize it. Then these more promising molecules could be produced, on a large scale, to treat the disease.
What is it?
This study works from passive transfer of immunity, which works with blood plasma transfusion from people cured of COVID-19. A liquid part of the blood, the plasma of patients who have healed is usually rich in antibodies against the disease. When this plasma enters the bloodstream of a sick person, in the passive transfer of immunity, the proteins (antibodies) present in it immediately begin to fight the new coronavirus. But for that, it is necessary to cure the blood of the patients.
What the Butantan Institute wants is not to need the blood of surviving patients (can you imagine the necessary number of donors to save all those infected?). To do this, researchers need to discover the exact antibodies that fight the coronavirus COVID-19 and thus be able to reproduce this compound on a large scale, as a synthetic medicine.
“In the case of monoclonal antibodies, a liquid made up of one or more antibodies selected among the most efficient is produced on a large scale, recombinantly, by cell cultures in what we call bioreactors”, explains researcher Ana Maria Moro and head of the study. . Currently, there are more than 70 monoclonal antibody-based biopharmaceuticals approved and in use worldwide, such as the fight against the Ebola virus.
How should it work?
For this purpose, the first stage of this research is to recruit convalescent volunteers from COVID-19. With the blood collected, scientists must perform a series of molecular biology processes to identify gene sequences that express neutralizing antibodies. Therefore, each antibody, which is found in donated plasmas, will be characterized in terms of its action against the virus, mainly in its neutralizing capacity.
Therefore, researchers should arrive at between one and three antibodies more efficiently in laboratory tests and then tested on animals. The next step is to understand how these successful antibodies can be reproduced, using various technical criteria. The results are considered for the selection of the best clones that can be produced, on a large scale, in a bioreactor. Only then will they be taken to preclinical and clinical trials, reaching human tests.
History
Coordinated by researcher Ana Maria Moro and supported by the São Paulo State Research Support Foundation (Fapesp), the Butantan Institute project uses a platform created for the development of human monoclonal antibodies (mAbs) for different diseases. “We started developing this platform in 2012 with human anti-tetanus mAbs, with the support of Fapesp, and we identified a composition of three antibodies that neutralize tetanus toxin. Then, we established an agreement with Rockefeller University, in the United States, under the coordination of Michel Nussenzweig, to generate cell lines for antizika mAbs, which were identified in his laboratory during the epidemic of the disease, in 2015, ”he explains to Agência Fapesp.
Source: Government of São Paulo.
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