Beyond Binding: Biologically Active Cyclic Peptides from mRNA Display
Research accelerates search for new drugs against COVID-19 and malaria
The study by Twan Hopstaken, researcher in the field of peptide drug development, shows that it is possible to select promising drug candidates from collections of more than a trillion random molecules in a much more targeted manner than before. This could significantly accelerate the development of new drugs for diseases for which no good treatment yet exists.
When discovering new drugs, scientists often look for molecules that bind to proteins involved in a disease. The problem is that many of these molecules do stick to a protein, but ultimately have no therapeutic effect. Hopstaken therefore focused on how precisely the active molecules can be extracted from huge molecular collections.
The results show that several new selection methods are successful. In one study, Hopstaken developed a collection of molecules based on a previously discovered COVID-19 drug. From this, a new candidate was selected that proved to be about a thousand times more potent than the original drug. In animal experiments, it also provided protection against infection.
The research also yielded promising results in the field of malaria. Using a modified selection technique, Hopstaken identified new drug candidates from a collection of more than a trillion molecules. By first excluding undesirable molecules, he was able to focus on compounds with the highest likelihood of efficacy. The candidates found work through a different mechanism than existing malaria drugs, offering perspective in the fight against increasing drug resistance.
In addition, Hopstaken developed an approach in which millions of potential drugs can be tested simultaneously for their biological activity. By combining this technique with existing selection methods, not only can molecules that bind to a target be found, but also directly compounds that actually have an effect. This makes the drug development process more efficient and accurate.
The improved COVID-19 drug is currently being further developed by the company VirXcel, with the goal of bringing a protective nasal spray to market. The initial application targets people with weakened immune systems, but in time the drug could have broader applications.
The discovered malaria candidates are also being further investigated by researchers and the Biomedical Primate Research Center. If efficacy is confirmed, they could contribute to new treatments against a disease that kills hundreds of thousands each year.
According to Hopstaken, the work shows that smart selection techniques increase the chances of finding effective drugs in huge molecular databases. This will allow the pharmaceutical industry in the future to develop faster and more targeted new treatments for infectious diseases and other conditions for which insufficient therapies are still available.
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