Integrative Approaches of Bioassay and Computational Analysis for Discovering Potential Bioactive Compounds and Predictive Toxicity.

Changes in eating habits are brought about by drastic changes in lifestyle and environment, and, it has been pointed out, are strongly involved in the increase in neurological diseases and onset of cancer in younger adult ages. There is a wide variety of chemical substances in food, and there is a need to analyze the effects of complex exposures on complex mechanisms of action and to develop methods for evaluating and predicting them. The power of molecular nutrition needs to create an integrated approach to human nutrition in line with the grand social challenges of diet-related illnesses. The current article aims to explore some of these areas where integration is appropriate. Therefore, in this symposium, we will introduce the contents of four performers who are conducting cutting-edge research. 1) Chemoprevention by vitamin A and its derivatives, 2) Toxicity prediction of natural compounds from a developing database of bioactive gradients from Kampo medicine, 3) Toxicity prediction of chemicals using pluripotent stem cells. 4) Detection of bioactive compounds in "Aji" or "Umami" in food. By detecting and predicting the biological activity and toxicity of chemical substances such as nutrients in foods, it will be possible to provide better molecular information on dietary components. In addition, we will introduce next-generation health and prevention methods.

Establishment of a Rapid Detection System for ISG20-Dependent SARS-CoV-2 Subreplicon RNA Degradation Induced by Interferon-α.

Inhaled nebulized interferon (IFN)-α and IFN-ß have been shown to be effective in the management of coronavirus disease 2019 (COVID-19). We aimed to construct a virus-free rapid detection system for high-throughput screening of IFN-like compounds that induce viral RNA degradation and suppress the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We prepared a SARS-CoV-2 subreplicon RNA expression vector which contained the SARS-CoV-2 5'-UTR, the partial sequence of ORF1a, luciferase, nucleocapsid, ORF10, and 3'-UTR under the control of the cytomegalovirus promoter. The expression vector was transfected into Calu-3 cells and treated with IFN-α and the IFNAR2 agonist CDM-3008 (RO8191) for 3 days. SARS-CoV-2 subreplicon RNA degradation was subsequently evaluated based on luciferase levels. IFN-α and CDM-3008 suppressed SARS-CoV-2 subreplicon RNA in a dose-dependent manner, with IC50 values of 193 IU/mL and 2.54 µM, respectively. HeLa cells stably expressing SARS-CoV-2 subreplicon RNA were prepared and treated with the IFN-α and pan-JAK inhibitor Pyridone 6 or siRNA-targeting ISG20. IFN-α activity was canceled with Pyridone 6. The knockdown of ISG20 partially canceled IFN-α activity. Collectively, we constructed a virus-free rapid detection system to measure SARS-CoV-2 RNA suppression. Our data suggest that the SARS-CoV-2 subreplicon RNA was degraded by IFN-α-induced ISG20 exonuclease activity.