A drug that is highly effective against Covid-19 – it is not yet on the market. A research team from Göttingen has now developed mini-antibodies that efficiently switch off the coronavirus SARS-CoV-2 and its dangerous new variants. This is announced by the Max Planck Institute (MPI) for Biophysical Chemistry and the University Medical Center Göttingen (UMG).
The people of Göttingen work with so-called nanobodies. According to the researchers, these bind and neutralize the virus up to 1000 times better than previously developed mini-antibodies. In addition, the scientists were able to perfect the mini-antibodies to such an extent that they are stable and withstand heat unscathed. “This unique combination makes it a very promising agent for treating Covid-19,” said MPI spokeswoman Carmen Rotte. Since nanobodies can be produced inexpensively and quickly in large quantities, they could meet the global demand for Covid-19 drugs. “They are now being prepared for clinical testing,” she says.
Antibodies can act like a drug
Antibodies help the immune system to fight off pathogens: They attach to viruses and neutralize them. Antibodies can be produced industrially and administered to those who are acutely ill. “Then they act like a drug, alleviate symptoms and shorten the course of the disease,” say the scientists. This is already in practice with hepatitis B or rabies. Antibodies are also used as an active ingredient in people infected with Covid 19. The problem: The industrial production of antibodies is so complex and expensive that demand cannot be met. Nanobodies could be a solution here.
The mini-antibodies developed by the Göttingen-based company have all the properties one would expect from an effective drug against Covid-19. “For the first time, they combine extreme stability and the highest level of effectiveness against the virus and its alpha, beta, gamma and delta variants,” says Dirk Görlich, Director at the MPI for Biophysical Chemistry.
At first glance, they hardly differ from mini-antibodies against Covid-19 from other laboratories. They all target the area of the spike protein that the virus uses to recognize its host cells and enter them. The nanobodies attach themselves to this binding domain, block it and thus prevent the virus from infecting cells.
“Our nanobodies can withstand temperatures of 95 degrees without being destroyed or forming aggregates,” explains Matthias Dobbelstein, professor and director of the Institute for Molecular Oncology at the UMG. “On the one hand, this tells us that they could remain active in the body long enough to be effective. On the other hand, temperature-stable nanobodies are much easier to manufacture, process and store. ”And further:“ Our simple nanobodies may be suitable for inhalation in order to contain the virus in the respiratory tract, ”says Dobbelstein. “Since they are very small, they can also easily penetrate the tissue and prevent the virus from spreading directly at the site of infection.”
According to the researchers, the binding efficiency is once again significantly improved in the “nanobody three-pack”. To do this, the researchers linked three identical nanobodies with one another. “With the three-pack, we bundle our strengths, so to speak: each of the three nanobodies ideally attaches itself to one of the three binding domains,” reports Thomas Güttler, a scientist in Görlich’s team. Another advantage: The three-part nanobodies are just big enough that the kidneys are likely to leave them in the blood and not excrete them in the urine within a few hours. This increases their retention time in the body and thus their effectiveness.
Alpacas provide blueprints for mini-antibodies
“Nanobodies come from alpacas and are much smaller and simpler than conventional antibodies,” reports Görlich. In order to produce the nanobodies against Sars-CoV-2, the team injected the three alpacas Britta, Nora and Xenia from the herd at the Göttingen MPI with part of the spike protein several times. The animals then formed antibodies against this protein part. After the last injection, the researchers took a small amount of blood from the animals. For the alpacas, their use was over; the next steps are carried out with the help of enzymes, bacteria, so-called bacteriophages and yeasts.
“Overall, the exposure to our animals is very low, comparable to a vaccination and blood test in humans,” explains Görlich. In the next step, the scientists obtained the blueprints for around a billion different nanobodies from the blood of the alpacas. Everything else for Görlich’s team was a laboratory routine that had been perfected over many years: the biochemists fished out the best from the initially astronomical number of nanobodies with bacteriophages. Researchers around Dobbelstein determined whether and how well the mini-antibodies switch off the coronavirus by simulating virus infections on cell cultures in the laboratory.
The Göttingen team is now preparing the nanobodies for therapeutic use. Dobbelstein emphasizes: “We want to test the nanobodies as quickly as possible for safe use as an active ingredient, so that they can benefit seriously ill people and those who have not been vaccinated or who cannot develop effective vaccination protection.”
From Britta Bielefeld