Significance of high-throughput screening assays in the drug discovery process

Author: Bennie George

The drug discovery process is challenging and costly. As diseases, viruses spread and patients increase, inventing new medicines becomes critical. Researchers are interested in discovering new drugs faster by employing higher-throughput screening methods. One approach to faster drug discovery is the high-throughput screening (HTS) approach, which has gained a lot of attention over the past few years.

High-throughput screening assays have different types and detection techniques, such as fluorescence resonance energy transfer (FRET), biochemical assays, fluorescence polarization (FP), homogeneous time-resolved fluorescence (HTRF), fluorescence correlation spectroscopy (FCS), fluorescence intensity distribution analytical (FIDA), Nuclear Magnetic Resonance (NMR), and research advances in three major technical fields including miniaturization, automation and robotics, and artificial intelligence, have shown great promise in accelerating drug discovery and its development process.

The combination of screening methods and bioinformatics enables efficient and rapid screening of potential drugs, resulting in faster drug discovery and more detailed exploration. Preliminary screening of the binding capacity of these compounds is the primary role of high-throughput screening methods. High-throughput screening processes often involve developing tests or assays in which potential compounds bind to proteins, resulting in visible changes that are automatically read by sensors. Typically, this change is achieved through the light emission of fluorophores in the reaction mixture. As a result of this process, the fluorophore is attached to the target protein in such a way that when the protein binds to another molecule, its ability to fluoresce is reduced (quenched). A different system then measures the difference in polarization, a property of light emitted by unbound and bound fluorophores.

The primary goal of a high-throughput screening process is to screen a library of compounds and help identify candidates that affect the target in the desired way. This phenomenon is called "hitting" or "leading." Typically, hits are achieved using a variety of technologies, including liquid handling equipment, plate readers, robotics, and data processing software. Today, automation and robotics are widely accepted in the drug discovery process and continue to make great strides in the field. Automated processes provide better process consistency and thus better data quality. Alternatively, automation not only allows scientists the freedom to leave and work on other tasks, but also allows for traceability if anything goes wrong. Automated processes minimize human error.

In conclusion, the HTS process is not particularly helpful for the identification of drugs because HTS cannot assess several properties that are critical to the development of new drugs. For example, the HTS method cannot assess properties such as bioavailability and toxicity. Instead, the primary role of HTS detection is to help identify "potential customers" and advise on their optimization. Therefore, the results of HTS analysis can help reveal the starting point for further steps in the drug discovery process, including drug design. HTS assays also help to understand the interaction or role of specific biochemical processes.

The HTS method should be accepted as a technique to scan biobanks quickly and efficiently, excluding compounds that have no effect in the analysis. Various academic institutions and major industries use high-throughput screening methods to screen large numbers of compounds every day. Various detection techniques such as FCS, NMR, HRTF, etc., are helpful for the screening of a large number of compounds.