High-throughput screening strategies for space-based radiation countermeasure discovery

As humanity begins to venture further into space, approaches to better protect astronauts from the hazards found in space need to be developed. One particular hazard of concern is the complex radiation that is ever present in deep space. Currently, it is unlikely enough spacecraft shielding could be launched that would provide adequate protection to astronauts during long-duration missions such as a journey to Mars and back. In an effort to identify other means of protection, prophylactic radioprotective drugs have been proposed as a potential means to reduce the biological damage caused by this radiation. Unfortunately, few radioprotectors have been approved by the FDA for usage and for those that have been developed, they protect normal cells/tissues from acute, high levels of radiation exposure such as that from oncology radiation treatments. To date, essentially no radioprotectors have been developed that specifically counteract the effects of chronic low-dose rate space radiation. This review highlights how high-throughput screening (HTS) methodologies could be implemented to identify such a radioprotective agent. Several potential target, pathway, and phenotypic assays are discussed along with potential challenges towards screening for radioprotectors. Utilizing HTS strategies such as the ones proposed here have the potential to identify new chemical scaffolds that can be developed into efficacious radioprotectors that are specifically designed to protect astronauts during deep space journeys. The overarching goal of this review is to elicit broader interest in applying drug discovery techniques, specifically HTS towards the identification of radiation countermeasures designed to be efficacious towards the biological insults likely to be encountered by astronauts on long duration voyages.