On the 4th September 2020, on the journal Nature Communications it was published a study that could become a milestone in the research for a therapy against COVID-19: researchers from Karolinska Institutet in Stockholm have discovered that a nanobody (called Ty1) isolated from alpacas is able to prevent the entry of SARS-CoV-2 (aka the new coronavirus) into human cells.
Some time ago I published an article in which I explained how the virus infects human cells: briefly, on the envelope of the virus there is a protein (called spike) capable of anchoring itself to the ACE2 receptor present on the surface of the cells. This anchoring process is the first, necessary step for infection to occur. The researchers found that a “mini” antibody (hence called nanobody) from alpaca is able to bind to the spike protein hook and prevent it from attaching to the ACE2 receptor, rendering the virus unable to infect.
But how were nanobodies against SARS-CoV-2 found in alpacas? Camelids spontaneously produce nanobodies and it was already known that some of them can be adapted for humans. This research began in February, when an alpaca was given the virus’s spike protein to stimulate the production of antibodies. This is the same strategy followed by vaccines: exposing an organism to isolated components of a virus (therefore not dangerous) to stimulate an antibody response. After 60 days, the alpaca was subjected to a blood test to assess the presence of antibodies, observing a strong immune response. Among the antibodies analyzed, one in particular had proved extremely effective in preventing SARS-CoV-2 infection and was renamed Ty1, in honor of Tyson, the alpaca that produced it, and which you can see in the photo below.
There are two huge advantages of using a nanobody instead of a normal antibody: the small size increases its specificity, and it can be produced on a large scale. Let’s see these two aspects in detail.
On the hook of the spike protein there are some appendages, called glycans, which “hide” it from the antibodies, protecting it. Given its small size (one tenth of a conventional antibody), the Ty1 nanobody, on the other hand, succeeds in finding its way to the active site of the hook, binding to it and preventing its interaction with ACE2.
It is difficult to exploit antibodies for therapeutic purposes because they cannot be produced in large amounts (they are usually isolated from mice, rats or rabbits, and the procedure takes a long time). Nanobodies, instead , can be produced in bacteria and it is possible to purify even more than 30 milligrams per liter of bacterial culture (a lot, trust me) in very short time. Another advantage is that working with bacteria instead of animals is much cheaper, as well as processive, representing the ideal condition for producing the drug currently most requested all over the world.
Because Ty1 seems to act in an extremely specific way, it is conceivable that it won’t cause side effects in therapy. To ascertain this, researchers are proceeding rapidly towards preclinical tests on animals, hoping to confirm the expectations, to move on then with clinical trials on humans.