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It all started with a scientific article published in a repository of publications that have not yet been peer-reviewed. Scientists call them prepublications. A group of Portuguese scientists read this prepublication and, based on this information, embarked on the adventure of developing a serological test. made in portugal.
In that pre-publication, the team of virologist Florian Krammer, from the Icahn School of Medicine at Mount Sinai Hospital in New York, United States, reported that they had isolated the sequences of a gene involved in the encoding of an important protein in the new coronavirus. as soon as Chinese scientists made its genome public on January 10. This viral protein is what gives air to the virus dotted with spikes on the surface. It is the peak protein, or spike.
The virus uses it to enter human cells, in particular a part of the protein called the “receptor-binding domain” (the receptor is found on the surface of human cells). The spike protein functions as the key; and the receiver is the lock. The virus uses the spike to adhere to the lock, in order to enter human cells and replicate.
Now, Florian Krammer’s team used the spike protein as an antigen, which is a substance that the body recognizes as foreign and triggers the production of antibodies (molecules) by the immune system against it. The scientists then took the genetic sequences of the spike protein, both in its entirety and part of the receptor-binding domain, and placed them inside a plasmid. Since plasmids are circular shaped DNA fragments, generally bacterial, which can be modified by adding new DNA fragments, they are a useful tool for inserting genetic material into target cells.
Using plasmids, they introduced the genetic sequence of the spike protein of the new coronavirus into human cells. And the cells began to produce these little bits of the virus.
In the end, on March 18, Florian Krammer’s team revealed to the whole world the protocol they followed in this pre-publication, in the medRxiv repository. In this way, anywhere in the world, other scientists were able to repeat the production of fragments of the virus that was causing a new disease (covid-19) and develop tests to detect antibodies in the blood. Since our immune system produces antibodies adapted to each pathogen, a test that detects them would help us understand and fight the new virus.
More: Florian Krammer’s team was available, in prepublication, to send to anyone who requested the plasmids developed in his lab. In many parts of the world, the goodwill of the American team was echoed. Even in Portugal, where five scientific research institutes have joined in a consortium (Serology4Covid) to develop, from these plasmids, a serological test.
Droplets of plasmids soaked in laboratory felt paper arrived in Portugal. One of the consortium partners, the Institute of Experimental and Technological Biology (IBET), in Oeiras, took these plasmids and began to produce enough spike protein from the new coronavirus, so that the other consortium partners could then develop the rest of the test.
Researcher Paula Alves
In Oeiras, as in the USA, plasmids were introduced into human cells. The biochemical engineer Paula Alves, director of IBET, explained in April to the PUBLIC that it was human cells that were going to manufacture the bits of the virus and why this was important in the good connection between the antigen and the antibody in a serological test. “Human cells are used as factories: with them we can produce the protein as close as possible to the reality of the virus when it infects cells.” The IBET director also pointed out that a serological test made in portugal it would avoid dependence on supply chains and allow the country to be self-sufficient.
The adventure of the trial is gaining industrial contours through Medinfar, a Portuguese pharmaceutical company, which manufactures for sale in the market. IBET will continue to produce antigen from team for Medinfar, in a commercial relationship between them, now as “raw material”, informs Mariana Almeida, responsible for the development and pharmaceutical innovation of that pharmaceutical group. What team Portuguese contains, explains Mariana Almeida, only the SARS-CoV-2 peak receptor binding domain. That is, a little bit of the virus.
