They are discovering a new “shortcut” to accelerate their development.

Most drugs are small molecules that affect the activity of proteins.

225 years have passed since the English language Edward Jenner (May 17, 1749 – January 26, 1823) introduced what is considered the first vaccine in history, but the intuition of this protection took several centuries to develop. Since Jenner’s experiment, progress has been impressive, culminating in the development of a Covid vaccine in a matter of months. However, one of the scientific advances that saved the most lives This also creates reluctance a phenomenon as old as the first vaccine.

However, vaccination or variolation, that is, the subcutaneous injection of antibodies that will then protect us from future infections, has such a wide field of activity that it will still surprise the world. Thus, these steps aimed at studying human proteins have found a new target and a “shortcut” that will allow their new and faster development. Recent research shows that small molecules are known that chemically bind them to so-called ligands. Ligands often represent an important starting point for drug development, but this knowledge gap seriously impedes the development of new drugs or vaccines.

Thus, researchers from the Research Center named after. Molecular Medicine CeMM from the Austrian Academy of Sciences, used and expanded a method to measure the binding activity of hundreds of small molecules to thousands of human proteins.

This massive effort identified tens of thousands of interactions. ligand protein which can now be used to develop chemicals and therapeutics such as vaccines. In addition, through machine learning and artificial intelligence, it can objectively predict how small molecules interact with all the proteins present in living human cells. These innovative results were published in the journal magazine The science All generated data and models are freely available to the scientific community.

Most drugs They are small molecules that influence activities squirrels. These small molecules, if properly understood, are also invaluable tools for characterizing protein behavior and conducting basic biological research.

Given these important functions, it is surprising that for more than 80% of all proteins, no binding small molecules have yet been discovered. This hinders the development of new drugs, vaccines and therapeutic strategiesbut it also impedes new biological understanding of health and disease.

To fill this gap, CeMM researchers, in collaboration with Pfizer, have expanded and expanded an experimental platform that allows them to measure how hundreds of small molecules with diverse chemical structures interact with all the proteins expressed in living cells. This resulted in a rich catalog of tens of thousands of interactions. protein ligand that can now be further optimized to provide a starting point for further therapeutic development.

In their study, the team led by CeMM principal investigator Georg Winter demonstrated this by developing small molecules that bind cellular transporters, components of the cellular degradation machinery, and understudied proteins involved in cell signaling. In addition, using large data setMachine learning and artificial intelligence models have been developed that can predict how additional small molecules interact with proteins expressed in living human cells.

“We were surprised to see how artificial intelligence and machine learning could improve our understanding of the behavior of small molecules in human cells. We hope that our catalog of small molecule-protein interactions and models AI partners can now provide the fastest path to drug discovery.“, says Georg Winter. To maximize potential impact and usefulness to the scientific community, all data and models are available free of charge through a web application.

Biggest achievement of the decade

Attenuation and inactivation are still used today, but the development of genetic engineering in the 1970s and 1980s paved the way for a new generation of synthetic vaccines, from those that use proteins or other components to those that use recombinant vectors, In many cases, harmless viruses act as vectors into which parts of the pathogen we want to be immunized against are introduced.

The last great technological leap began to take shape in the 90s thanks to several researchers, among whom Hungarian biochemistry stands out. Katalin Kariko and American immunologist Drew Weissman. It involves introducing instructions into the body in the form of messenger RNA (mRNA) so that the body itself can produce a vaccine – an antigen that stimulates an immune response. While new vaccine platforms can be tailored to new viruses, mRNA platforms are so controllable and versatile that they can create a vaccine in just a few weeks, as demonstrated by Moderna and BioNTech-Pfizer against Covid. “MRNA vaccines are the greatest advance of the last decade and a huge part of the future of vaccines,” said an infectious disease specialist at California State University. Virginia William Petrie.