A series of novel quinazolinone sulfide derivatives containing a dithioacetal moiety were designed and synthesized using Tomato chlorosis virus coat protein (ToCVCP) as a potential drug target, and the inhibitory effect of ToCV was systematically evaluated in vitro and in vivo. The experimental results showed that most of the compounds presented a strong affinity. Notably, the binding abilities of compounds D8 and D16 to ToCVCP both reached a micromolar level, which were 0.19 and 0.83 μM, respectively. The relative expression level of ToCVCP gene was detected using real-time quantitative polymerase chain reaction in Nicotiana benthamiana. Compounds D8 and D16 significantly reduced the relative expression level of ToCVCP gene by 93.34 and 83.47%, respectively, which were better than those of conventional antiviral agents. This study lays a good foundation for the structural design and modification of quinazolinone sulfide derivatives as anti-ToCV drugs.Manganese (Mn) is an essential element that participates in several biological processes. Mn serves as a cofactor for several enzymes, such as glutamine synthetase and oxidoreductases, that have an important role in the defense of the organisms against oxidative stress. The diet is the main source of Mn intake for humans, and adequate daily intake levels for this metal change with age. Moreover, in higher amounts, Mn may be toxic, mainly to the brain. Here, we provide an overview of Mn occurrence in food, addressing its bioaccessibility and discussing the dietary standard and recommended intake of Mn consumption. In addition, we review some mechanisms underlying Mn-induced neurotoxicity.Plasma disinfection using low temperature atmospheric pressure plasma is widely studied in many applications, and the use of plasma-treated water (PTW) for disinfection is being developed by many researchers. Exposing plasma to water supplies and preserves reactive oxygen and nitrogen species (RONS) in the water, and this PTW exhibits bactericidal activity. In our previous study, it was revealed that peroxynitric acid (O2NOOH, PNA) was the dominant bactericidal component in PTW. PNA can be easily synthesized without plasma treatment, and the physicochemical properties of PNA have been well analyzed. As the application of PNA in fields related to medicine and biology has not been reported, a basic study on the behavior of PNA is required. In this study, the bactericidal activity of PNA and its reactivities with 20 naturally occurring amino acids were evaluated to understand its reaction mechanism with biomolecules. Interestingly, PNA exhibited 10-6 times lower reactivities with amino acids when compared with hypochlorous acid and other RONS, although its bactericidal activity was 310 times higher than that of sodium hypochlorite. In addition, the reactivity of PNA with methionine was over 100 times higher than that with other amino acids, indicating that the reactions of PNA with amino acids are highly specific. check details No other oxidants have been reported to react selectively with only methionine. As methionine is involved in specific activities in the cells, the unique reaction profile of PNA was examined in the context of biological systems.Getting information about the fate of immobilized enzymes and the evolution of their environment during turnover is a mandatory step toward bioelectrode optimization for effective use in biodevices. We demonstrate here the proof-of-principle visual characterization of the reactivity at an enzymatic electrode thanks to fluorescence confocal laser scanning microscopy (FCLSM) implemented in situ during the electrochemical experiment. The enzymatic O2 reduction involves proton-coupled electron transfers. Therefore, fluorescence variation of a pH-dependent fluorescent dye in the electrode vicinity enables reaction visualization. Simultaneous collection of electrochemical and fluorescence signals gives valuable space- and time-resolved information. Once the technical challenges of such a coupling are overcome, in situ FCLSM affords a unique way to explore reactivity at the electrode surface and in the electrolyte volume. Unexpected features are observed, especially the pH evolution of the enzyme environment, which is also indicated by a characteristic concentration profile within the diffusion layer. This coupled approach also gives access to a cartography of the electrode surface response (i.e., heterogeneity), which cannot be obtained solely by an electrochemical means.The protein folding problem has been studied in the field of molecular biophysics and biochemistry for many years. Even small changes in folding patterns may lead to serious diseases like Alzheimer’s or Parkinson’s where proteins are folded either too quickly or too slowly. Molecular dynamics (MD) is one of the tools used to understand how proteins fold into native conformations. While it captures sequences of conformations that lead over time to the folded state, limitations in simulation timescales remain problematic. Although many approaches have been suggested to speed-up the simulation process using rapid changes in temperature or pressure, we propose a rational approach, Greedy-proximal A* (GPA*), derived from path finding algorithms to explore the supposed shortest-path folding pathway from the unfolded to a given folded conformation. We introduce several new protein structure comparison metrics based on the contact map distance to help mitigate the challenges faced by “standard” metrics. We test our approach on proteins which represent the two main types of secondary structure a) the Trp-Cage Miniprotein Construct TC5b (1L2Y) which is a short, fast-folding protein that represents alpha-helical secondary structure formed because of a locked triptophan in the middle, b) the immunoglobulin binding domain of streptococcal protein G (1GB1), containing an alpha-helix and several beta-sheets, and c) the chicken villin subdomain HP-35, N68H protein (1YRF) – one of the fastest folding proteins which forms three alpha-helices. We compare our algorithm to Replica-Exchange Molecular Dynamics (REMD) and Steered Molecular Dynamics (SMD) methods which represent the main algorithms used for accelerating folding proteins with MD. We find that GPA* not only reduces the computational time needed to obtain the folded conformation without adding artificial energy bias, but also makes it possible to generate trajectories which contain minimal motions needed for the folding transition.