Identification of potential inhibitors of omicron variant of SARS-Cov-2 RBD based virtual screening, MD simulation, and DFT.

Emergence of the SARS-CoV-2 Omicron variant of concern (VOC; B.1.1.529) resulted in a new peak of the COVID-19 pandemic, which called for development of effective therapeutics against the Omicron VOC. The receptor binding domain (RBD) of the spike protein, which is responsible for recognition and binding of the human ACE2 receptor protein, is a potential drug target. Mutations in receptor binding domain of the S-protein have been postulated to enhance the binding strength of the Omicron VOC to host proteins. In this study, bioinformatic analyses were performed to screen for potential therapeutic compounds targeting the omicron VOC. A total of 92,699 compounds were screened from different libraries based on receptor binding domain of the S-protein via docking and binding free energy analysis, yielding the top 5 best hits. Dynamic simulation trajectory analysis and binding free energy decomposition were used to determine the inhibitory mechanism of candidate molecules by focusing on their interactions with recognized residues on receptor binding domain. The ADMET prediction and DFT calculations were conducted to determine the pharmacokinetic parameters and precise chemical properties of the identified molecules. The molecular properties of the identified molecules and their ability to interfere with recognition of the human ACE2 receptors by receptor binding domain suggest that they are potential therapeutic agents for SARS-CoV-2 Omicron VOC.

Training, testing and benchmarking medical AI models using Clinical AIBench

AI technology has been used in many clinical research fields, but most AI technologies are difficult to land in real-world clinical settings. In most current clinical AI research settings, the diagnosis task is to identify different types of diseases among the given ones. However, the diagnosis in real-world settings needs dynamically developing inspection strategies based on the existing resources of medical institutions and identifying different kinds of diseases out of many possibilities. To promote the development of different clinical AI technologies and the implementation of clinical applications, we propose a benchmark named Clinical AIBench for developing, verifying, and evaluating clinical AI technologies in real-world clinical settings. Specifically, Clinical AIBench can be used for: (1) Model training and testing: Researchers can use the data to train and test their models. (2)Model evaluation: Researchers can use Clinical AIBench to objectively, fairly, and comparably evaluate various models of different researchers. (3) Clinical value evaluation: Researchers can use the clinical indicators provided by Clinical AIBench to evaluate the clinical value of models, which will be applied in real-world clinical settings. For convenience, Clinical AIBench provides three different levels of clinical settings: restricted clinical setting, which is named closed clinical setting, data island clinical setting, and real-world clinical setting, which is called open clinical setting. In addition, Clinical AIBench covers three diseases: Alzheimer’s disease, COVID-19, and dental. Clinical AIBench provides python APIs to researchers. The data and source code are publicly available from the project website https://www.benchcouncil.org/clinical_aibench/.