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Drug discovery has entered a new period of vigorous development with advanced technologies such as DNA-encoded library (DEL) and artificial intelligence (AI). The previous DEL-AI combination has been successfully applied in the drug discovery of classical kinase and receptor targets mainly based on the known scaffold. So far, there is no report of the DEL-AI combination on inhibitors targeting protein-protein interaction, including those undruggable targets with few or unknown active scaffolds. Here, we applied DEL technology on the T cell immunoglobulin and ITIM domain (TIGIT) target, resulting in the unique hit compound 1 (IC50 = 20.7 μM). Based on the screening data from DEL and hit derivatives a1-a34, a machine learning (ML) modeling process was established to address the challenge of poor sample distribution uniformity, which is also frequently encountered in DEL screening on new targets. In the end, the established ML model achieved a satisfactory hit rate of about 75% for derivatives in a high-scored area.

Vesicular stomatitis virus G glycoprotein (VSV-G) has been widely used for pseudotyping retroviral, lentiviral, and artificial viral vectors. The objective of this study was to establish a potential approach for large-scale production of VSV-G. To this end, VSV-G was cloned with an N-terminal His-tag into

The zebrafish has become an established model organism for the study of hearing and balance systems in the past two decades. The classical approach to examine hair cells is to use dye to conduct selective staining, which shows the number and morphology of hair cells but does not reveal their function. Startle response is a behavior closely related to the auditory function of hair cells; therefore it can be used to measure the function of hair cells. In this study, we developed a device to measure the startle response of zebrafish larvae. By applying various levels of stimulus, it showed that the system can discern a 10 dB difference. The hair cell in zebrafish can regenerate after damage due to noise exposure or drug treatment. With this device, we measured the startle response of zebrafish larvae during and after drug treatment. The results show a similar trend to the classical hair cell staining method. The startle response was reduced with drug treatment and recovered after removal of the drug. Together it demonstrated the capability of this behavioral assay in evaluating the hair cell functions of fish larvae and its potential as a high-throughput screening tool for auditory-related gene and drug discovery.