BGN Technologies, BGU's technology transfer company has introduced a novel method developed by BGU researchers for screening and detecting new antibiotics.
The ribosome, the protein-manufacturing machinery of all living cells, is one of the main targets of antibiotics. Inhibition of ribosomal activity in bacterial cells results in depletion of essential proteins and finally in cell death. However, the ribosome is a huge complex containing both RNA molecules and several proteins, therefore identifying drugs that will inhibit its activity is a challenging task.
Dr. Barak Akabayov (pictured above), from BGU's Department of Chemistry, and his team developed a novel method to design new antibiotics that target a small RNA region in the ribosome, called the peptidyl transferase center (PTC). Focusing on this region allows quick and efficient drug screening and drug design.
The technology combines empirical screening of small molecular fragments that bind the PTC using Nuclear Magnetic Resonance (NMR), with machine learning algorithms that enable the computational design of novel drugs based on the small molecular fragments. The researchers screened a collection of 1000 molecule fragments to find a subset that binds the PTC RNA. Then, using the characteristics of the fragment subset and computational methods they screened a library of 230 million molecules in order to select larger molecules that contain these fragments and are still predicted to bind the PTC and inhibit ribosome function. Two molecules were eventually identified and their ability to inhibit ribosome function was experimentally validated. The findings were published in Chemical Science[i].
"The novel method developed by Dr. Akabayov provides an efficient, fast and cost-effective route to identifying novel antibiotics that inhibit the ribosome," said Dr. Galit Mazooz Perlmuter, Senior VP Business Development Bio-Pharma at BGN Technologies. "This is extremely important in light of the looming antibiotic-resistance crisis that is predicted by the WHO and other health agencies worldwide. Following the financial support of the Israel Innovation Authority that sponsored this research and the promising results to date, we are now seeking an industry partner for further development of this patent-pending invention."
"With the constant decline in antibiotic agents approved each year by the FDA, there is an urgent need for new antibiotics to address the approaching antibiotic-resistance crisis," Dr. Akabayov, added. "It is important to point out that our workflow design is applicable not only to antibiotics targeting the ribosome RNA but also for other RNA targets, such as RNA viruses responsible for diseases such as hepatitis or HIV, as well as for other conditions such as cancer."