Respiratory Syncytial Virus (RSV) is a common virus that infects children and adults. It is responsible for thousands of outpatient visits (e.g., emergency room/primary care physician), hospitalizations and can result in death (J Pediatr Pharmacol Ther. 2009)
RSV infection has been an unmet medical need for many years. Small molecules that directly bind or interfere with viral protein did not show sufficient efficacy in preclinical and clinical settings. The main problem in targeting viral proteins is that RSV, as many viruses, is not only a “hard target” but also a “moving target”. The virus mutates rapidly rendering the drug ineffective. A new strategy for the discovery of anti-viral drugs Instead of targeting the viral protein that is subject to mutations, we focus on cellular targets that viruses hijack and use to control the translation of their proteins. These targets are in the host cell and therefore are not impacted by the mutation of the virus itself.
During protein translation, ribosomes chain amino acids that are carried by tRNAs molecules. Anima’s Protein Synthesis Monitoring (PSM) technology uses fluorescently labelled tRNA pairs, specifically selected for each target protein. When such a labeled pair enters the ribosome, it emits a light pulse. The light pulses tell us when, where and how much of the target proteins being made by ribosomes, in real time.
We used labeled tRNA pairs to monitor the translation of RSV’s Immediate early genes (IEGs). The dots of light represent actively translating ribosomes of viral proteins in these images. At increasing virus concentration, stronger light signal is observed (yellow spots).
Anima's PSM technology for the detection of RSV translation was validated by using a known RSV fusion inhibitor. We detect inhibition of RSV translation when cells were treated with fusion inhibitor, this indicates that our technology may identify RSV inhibitors which exhibit additional mode of actions, not only translation inhibitors.
A 100K library of compounds was screened in Anima’s RSV assay. Compounds which reduce RSV translation have been identified (see below), and are currently undergoing hit optimization.