Adapting high-throughput screening methods and assays for biocontainment laboratories

Area of Science:

• Infectious disease research
• Drug discovery and development
• Biosafety and containment

Background:

• High-throughput screening (HTS) is crucial for drug discovery but has historically focused less on infectious agents.
• Emerging infectious diseases and global mobility necessitate new drug development strategies.
• Conducting HTS with wild-type pathogens presents unique challenges, especially at higher biosafety levels (BSL).

Purpose of the Study:

• To review the feasibility and requirements of adapting high-throughput screening (HTS) for drug discovery targeting high-containment pathogens.
• To outline the specific challenges and considerations for executing HTS in high-level biocontainment laboratories.
• To provide an overview of the necessary infrastructure and protocols for HTS in BSL-4 environments.

Main Methods:

• Review of existing literature and case studies on HTS campaigns involving infectious agents.
• Analysis of HTS adaptations for different biosafety levels (BSL-2, BSL-3, and BSL-4).
• Examination of pilot screens conducted with Nipah and Ebola viruses in BSL-4 settings.

Main Results:

• HTS campaigns using wild-type pathogens are increasingly common, moving beyond surrogate targets.
• Successful HTS has been demonstrated for bacterial and viral pathogens at BSL-2 and BSL-3.
• Pilot HTS studies for Nipah and Ebola viruses in BSL-4 environments confirm the safety and feasibility of high-containment screening.

Conclusions:

• High-throughput screening (HTS) can be safely and effectively conducted in high-containment biocontainment laboratories for emerging infectious diseases.
• Adapting HTS for high-containment pathogens requires specific considerations regarding safety, infrastructure, and methodology.
• This approach is vital for developing novel therapeutics against serious public health threats posed by highly pathogenic agents.