Performance Analysis of Single-Well Enhanced Geothermal System for Building Heating

Deep borehole heat exchanger (DBHE) technology does not depend on the existence of hot water reservoir and can be used in various regions. However, the heat extraction from DBHE can hardly be improved due to poor thermal conductivity of rocks. Here, a single-well enhanced geothermal system (SWEGS) is proposed, which has a larger heat-exchange area of artificial reservoir created by fracturing hydrothermal technology. We find that, due to heat convection between rocks and fluid, the extracted thermal output for SWEGS is 4772.73 kW, which is 10.64 times of that of DBHE. By changing the injection water temperature, volume flow rate, and artificial reservoir volume, it is easy to adjust the extracted thermal output to meet the requirement of building thermal loads varying with outdoor air temperature. Understanding these will enable us to better apply SWEGS technology and solve the fog and haze problem easily and efficiently

Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking

<div><p>The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe the discovery of novel potent HCV NS5B polymerase inhibitors by employing a virtual screening (VS) approach, which is based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In the RB-VS stage, after feature selection, a model with 16 descriptors was used. In the PB-VS stage, six energy-based pharmacophore (e-pharmacophore) models from different crystal structures of the NS5B polymerase with ligands binding at the palm I, thumb I and thumb II regions were used. In the DB-VS stage, the Glide SP and XP docking protocols with default parameters were employed. In the virtual screening approach, the RB-VS, PB-VS and DB-VS methods were applied in increasing order of complexity to screen the InterBioScreen database. From the final hits, we selected 5 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 5 compounds were found to inhibit NS5B polymerase with IC₅₀ values of 2.01–23.84 μM and displayed anti-HCV activities with EC₅₀ values ranging from 1.61 to 21.88 μM, and all compounds displayed no cellular cytotoxicity (CC₅₀ > 100 μM) except compound N2, which displayed weak cytotoxicity with a CC₅₀ value of 51.3 μM. The hit compound N2 had the best antiviral activity against HCV, with a selective index of 32.1. The 5 hit compounds with new scaffolds could potentially serve as NS5B polymerase inhibitors through further optimization and development.</p></div

Redocked binding modes of the co-crystalized inhibitors in the active site of NS5B polymerase.

<p>(A-B) the palm I region, (C-D) the thumb I region, (E-F) the thumb II region.</p

Structures of the 5 hit compounds.

<p>Structures of the 5 hit compounds.</p

E-pharmacophore hypotheses with energetically favorable sites from the six crystal structures.

<p>Pink sphere represents hydrogen-bond acceptor (A); orange ring represents aromatic ring (R); blue sphere represents hydrogen-bond donor (D); red sphere represents negatively ionizable (N); green spheres represent hydrophobic (H).</p

E-pharmacophore features and the scores for each feature in e-pharmacophore hypotheses generated from the six crystal structures.

<p>E-pharmacophore features and the scores for each feature in e-pharmacophore hypotheses generated from the six crystal structures.</p

Antiviral activity and cytotoxicity of the 5 hits.

<p>Antiviral activity and cytotoxicity of the 5 hits.</p

The binding poses of compound N1 –N5 in the respective binding pocket of NS5B polymerase.

<p>(A) N1; (B) N2; (C) N3; (D) N4; (E) N5. Potential hydrogen bonding interaction are shown as dashed lines.</p

Validation of the six e-pharmacophore hypotheses.

<p>Validation of the six e-pharmacophore hypotheses.</p