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Assessment of High-Throughput Screening (HTS) Methods for High-Consequence Pathogens

Brian M Friedrich, Corinne E Scully, Jennifer M Brannan, Monica M Ogg, Sara C Johnston, Lisa E Hensley, Gene G Olinger and Darci R Smith

Currently, there are no Food and Drug Administration (FDA)-approved antiviral drugs or therapeutics for many of the biosafety level three (BSL-3) and four (BSL-4) pathogens. Many of these high-consequence pathogens, including Venezuelan equine encephalitis virus (VEEV), Ebola virus (EBOV), Marburg virus (MARV), and Lassa virus (LASV), are classified as biothreat agents and the development of therapeutic treatments for these diseases is an important area of research. In recent years, high-throughput screening (HTS) assays have become an effective and robust tool used for drug and therapeutic discovery. There are several types of HTS methods available, including targeted screening, diversity and high-content screening, and RNA interference (RNAi). These screens have been used effectively with a number of BSL-2 pathogens, but present unique challenges for the BSL-3/4 pathogens due to the requirement for higher level biocontainment facilities as well as biosurety requirements. Addressing and overcoming these challenges is essential for the proper adaptation of HTS into higher biocontainment facilities. In this article, we will discuss the advantages and disadvantages of each of the aforementioned HTS methods in the context of BSL-3/4 containment.