In Silico Modeling of Lovastatin Analogues as Inhibitors of HIV-1 Nef Protein
Currently, no method can completely eliminate the human immunodeficiency virus (HIV) in an infected person. HIV employs an accessory protein called Nef that forms a complex with cellular AP-1, preventing detection of HIV-infected cells. Lovastatin has been recently identified to inhibit the formation of said Nef-AP-1 complex, but its effective concentration is remarked to be far higher than other Nef inhibitors. This study aims to develop a modified lovastatin molecule exhibiting higher binding affinity to the HIV-1 Nef protein than lovastatin in silico. Modified lovastatin molecules based on the interaction map of lovastatin with Nef were modeled, and flexible ligand-flexible receptor docking to the Nef binding site was performed using AutoDock Vina. Residues within the Nef binding site identified by Liu et al. (2019) to be crucial (Glu-63, Val-66, Phe-68, Asp-108, Leu-112, Tyr-115) were set as flexible. Fragment-based drug design was utilized to append molecular fragments to lovastatin in order to maximize its interactions with said crucial residues. From the fragment-based approach, molecule F4 ((1S,3S)‐8‐{2‐[(2R,4R)‐4‐chloro‐6‐oxooxan‐2‐yl]ethyl}‐3‐(hydroxymethyl)‐7‐methyl‐1,2,3,4‐tetrahydronaphthalen‐1‐yl 4‐aminobenzoate) exhibited a binding affinity of -9.0 kcal/mole, and its estimated IC50 ranges between 0.25-0.51 μM which is at least 7.5 times lower than the reported IC50 of lovastatin from literature. This study presents insights on the key modifications to improve lovastatin as an HIV-1 Nef inhibitor and pertinent information about the Nef binding site for future drug development studies.
Synthesize Sodium Sesquicarbonate and Increase Yield
In order to recycle disposable diapers, we investigated the conditions where sodium sesquicarbonate (Chemical formula Na2CO3・ NaHCO3・ 2H2O hereinafter called sesqui) precipitates selectively from sodium carbonate and the conditions for high yield. For the selective precipitation of sesqui, we defined the time required for the reaction solution to pass through the sesqui precipitation area in the Na2CO3-NaHCO3-H2O phase diagram (45°C) as Δ t. As a result, we revealed that Δt is involved in the selective precipitation of sesqui, and that we can synthesize sesqui without the expensive addition of L-Arginine as used in a previous research. Also, we proposed the “Stay method”, in which the supply of CO2 is stopped for 30 minutes to the lengthen the Δ t, and found that we could synthesize sesqui selectively even under conditions in which sodium bicarbonate is likely to be precipitated as well. Regarding the high yield of sesqui, the yield was greatly improved by the common ion effect of Na by adding NaOH to the reaction solution, sesqui synthesis by repeated reactions with CO2, and sesqui recovery by adding the anti-solvent ethanol, reaching a sesqui conversion rate of 95%. This means 109 g of sesqui can be synthesized from 100 g of Na2CO3. Moreover, we confirmed that these synthesized samples have almost the same detergency as commercial sesqui. We did a test calculation to reveal the usefulness of this research. First, if diaper recycling technology is put into practical use and all used diaper waste in Saijo City can be recycled, a reduction of 534 t/year of used diaper waste can be expected. This corresponds to a 2.3% reduction in Saijo City's waste output. From the ash that would ultimately remain after being recycled, we expect up to 35.3 t/year of synthesized sesqui using our experimental method. In addition, a CO2 reduction of 8.2 t/year is possible in the process, which is about equivalent to the volume of one gymnasium.
Reducibility of Silver ions by the Charcoal: Regarding Mechanisms, Art, and Liquid Waste Management
We elucidated the cause of the phenomenon, in which silver deposits on a bamboo charcoal when the bamboo charcoal is soaked in an AgNO3 water solution. From the experimental results, we considered that the hydrogen which is generated while the bamboo wood is carbonized is chemisorbed as C-H bonds on the surface edge of charcoal (the end of the carbon), and that these hydrogen atoms become hydrogen ions,which then reduce the silver ions and deposit silver. In addition, we created a graph of the mass of deposited silver versus the mass of charcoal, and the graph showed that the mass of deposited silver was strongly correlated with the surface area calculated from the mass of the charcoal. Besides, we showed that charcoal can be used in applications for the treatment of inorganic liquid waste, depositing metals from inorganic liquid waste by bamboo charcoals. Also, the charcoal is used for interior decoration because of its deodorizing effect and beauty. In our study, we create a work of art used silverdeposited charcoal with a motif of Karesansui (Traditional Japanese rock garden).
Discussion for Titanium Peroxides and Their Application for Dealing with Zombie Shrimp Issue
Food safety was an important issue recently. Today sodium percarbonate was used to fake the vitality of shrimps to earn a good sell. However, it may cause harm to health because of the peroxides left over. To handle this problem, we set up two goals to achieve: detecting them and then removing them. In the past, the titration skill was an easy method for determining the concentration of H2O2. It not only spent too much time but also resulted in errors commonly. In this research, titanium sulfate and citric acid were used to prepare the colorimetric reagent. To measure the peroxides in water, several factors were controlled and the SOP for detecting and the calibration line for peroxides finally established. In practical, we turned the colorimetric reagent into the fast test paper which was easily for use. The other part of this research was to clear up the peroxides in water. We use titanium sulfate, hydrogen peroxide and citric acid as starting material via hot-bath method to prepare the nano-photocatalyst of titanium dioxide. Since the powder was inconvenient to deal with large amount of water. The powder-like TiO2 was further made into ball-shaped TiO2 in favor of water treatment and reuse. It was found that the photocatalytic performance of ball-shaped TiO2 was effective to be on duty for removal of the peroxides. In summary, this research provided two techniques to deal with the zombie shrimp. The novel method for synthesis of TiO2 catalyst and the preparation of colorimetric reagent for fast test paper were all in low cost. They had great potential to develop in marketing demand.