The main protease (Mpro) of the novel coronavirus SARS-CoV-2, which has caused the COVID-19 pandemic, is responsible for the maturation of its key proteins. Thus, inhibiting SARS-CoV-2 Mpro could ...prevent SARS-CoV-2 from multiplying. Because new inhibitors require thorough validation, repurposing current drugs could help reduce the validation process. Many recent studies used molecular docking to screen large databases for potential inhibitors of SARS-CoV-2 Mpro. However, molecular docking does not consider molecular dynamics and thus can be prone to error. In this work, we developed a protocol using free energy perturbation (FEP) to assess the potential inhibitors of SARS-CoV-2 Mpro. First, we validated both molecular docking and FEP on a set of 11 inhibitors of SARS-CoV-2 Mpro with experimentally determined inhibitory data. The experimentally deduced binding free energy exhibits significantly stronger correlation with that predicted by FEP (
R
= 0.94 ± 0.04) than with that predicted by molecular docking (
R
= 0.82 ± 0.08). This result clearly shows that FEP is the most accurate method available to predict the binding affinity of SARS-CoV-2 Mpro + ligand complexes. We subsequently used FEP to validate the top 33 compounds screened with molecular docking from the ZINC15 database. Thirteen of these compounds were predicted to bind strongly to SARS-CoV-2 Mpro, most of which are currently used as drugs for various diseases in humans. Notably, delamanid, an anti-tuberculosis drug, was predicted to inhibit SARS-CoV-2 Mpro in the nanomolar range. Because both COVID-19 and tuberculosis are lung diseases, delamanid has higher probability to be suitable for treating COVID-19 than other predicted compounds. Analysis of the complexes of SARS-CoV-2 Mpro and the top inhibitors revealed the key residues involved in the binding, including the catalytic dyad His14 and Cys145, which is consistent with the structural studies reported recently.
Free Energy Pertubation (FEP) can be used to accurately predict the binding affinity of a ligand to the main protease (Mpro) of the novel coronavirus SARS-CoV-2.
The 2,3,7,8-tetrachlorodibenzodioxin (TCDD), a contaminant in Agent Orange released during the US–Vietnam War, led to a severe environmental crisis. Approximately, 50 years have passed since the end ...of this war, and vegetation has gradually recovered from the pollution. Soil bacterial communities were investigated by 16S metagenomics in habitats with different vegetation physiognomies in Central Vietnam, namely, forests (S0), barren land (S1), grassland (S2), and developing woods (S3). Vegetation complexity was negatively associated with TCDD concentrations, revealing the reasoning behind the utilization of vegetation physiognomy as an indicator for ecological succession along the gradient of pollutants. Stark changes in bacterial composition were detected between S0 and S1, with an increase in Firmicutes and a decrease in Acidobacteria and Bacteroidetes. Notably, dioxin digesters
Arthrobacter
,
Rhodococcus
,
Comamonadaceae
, and
Bacialles
were detected in highly contaminated soil (S1). Along the TCDD gradients, following the dioxin decay from S1 to S2, the abundance of Firmicutes and Actinobacteria decreased, while that of Acidobacteria increased; slight changes occurred at the phylum level from S2 to S3. Although metagenomics analyses disclosed a trend toward bacterial communities before contamination with vegetation recovery, non-metric multidimensional scaling analysis unveiled a new trajectory deviating from the native state. Recovery of the bacterial community may have been hindered, as indicated by lower bacterial diversity in S3 compared to S0 due to a significant loss of bacterial taxa and recruitment of fewer colonizers. The results indicate that dioxins significantly altered the soil microbiomes into a state of disorder with a deviating trajectory in restoration.
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•Solvent-free synthesis of 2-arylbenzoxazole was catalyzed by Zr/Hf-MOFs.•MOF catalytic activity was enhanced by microwave irradiation.•Mechanism of ring open pathway acylation ...reaction under Zr/Hf-MOFs catalysis was described.•Catalytic activity of Zr-MOFs and Hf-MOFs was compared by experimental and computational studies.•The catalysts was recovered and reused in the reaction under microwave irradiation.
Zirconium- and hafnium-based metal–organic frameworks which constructed by 12-coordinated clusters and 6-coodinated clusters were shown to be highly effective heterogeneous catalysts for the ring opening acylation of benzoxazole to 2-arylbenzoxazole under solvent free conditions. Owning the wide opening spaces structures and inherent formate sites, MOFs based on 6-connected Zr6/Hf6 node were able to identify a significantly enhanced yield in Brønsted acid catalyzed reactions under conventional heating and microwave irradiation. In addition, the detailed mechanism of active sites of the ring opening acylation reaction was confirmed by employing of density functional theory (DFT) calculations.
In this study, we aim to develop an efficient, eco-friendly and cost-effective electrolyte solvent mixture for Dye-sensitized Solar Cells (DSCs) by using a deep eutectic solvent (DES). A high-purity ...choline chloride–phenol DES was synthesized and characterized by Fourier-transform infrared and nuclear magnetic resonance spectroscopy; thermogravimetric analysis and differential scanning calorimetry. The resulting product was mixed with acetonitrile, a typical volatile electrolyte solvent, at various ratios for use as electrolyte in DSCs. The photovoltaic parameters (Jsc, Voc, fill factor, efficiency) of these DSC devices were monitored to investigate their long-term performance. The performance of DES-added cells was initially less efficient, but more stable after more than 1000 h, compared to that of the DES-free cells. DES helped to stabilize and improve the photovoltaic performance of DSCs, particularly the short circuit current, due to the effect of the choline and phenol groups of DES binding on the TiO2 surface, as shown by the density functional theory (DFT) calculation. The optimal results were achieved with electrolyte containing 20% DES (efficiency = 6.9% with stable performance for more than 1000 h).
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•An eco-friendly DES mixed with liquid electrolyte for stable DSC performance.•Efficiency of DSC with 20% DES increased from 6.92% to 7.75% after 1300 h.•Co-adsorption of choline and phenyl on surface of TiO2 was calculated by the DFT.•The DES helped stabilize the current and improve the voltage of the DSC devices.
In this survey, food items were collected from vicinities of Bien Hoa and Da Nang airbase and determined for polychloro-dibenzo-dioxins and polychloro-dibenzo-furans (PCDD/Fs) to assess their ...accumulation, distribution in the local food items, and risk of PCDD/F exposure through consumption of the local foods. Dioxin compounds were determined using isotope dilution method which is slightly modified from US-EPA method 1613B. The dioxin concentration was the highest in fish followed by eggs, chicken, meat (pork and beef), and vegetables. Particularly, in Bien Hoa airbase, the mean concentrations of dioxin on TEQ and lipid basis (except for vegetables) were 26 pg/g for fish, 13 pg/g for eggs, 20 pg/g for chicken, 4.5 pg/g for meat, and 0.34 pg/g fresh wt for vegetables. In Da Nang airbase, the mean levels of dioxin on TEQ and lipid basis were slightly lower, 12.9 pg/g for fish, 8.7 pg/g for eggs, 5.9 pg/g for chicken, 6.7 pg/g for meat, and 0.17 pg/g for vegetables. It has been interesting to observe that free-range chicken expose to higher level of dioxin than caged chicken. In some free-range chicken, the portion of 2,3,7,8-TCDD was relatively high and implying recent exposure to dioxin.
Concentrations of seven polybrominated diphenyl ethers (PBDEs) congeners were determined in surface sediments collected from several rivers and lakes in Hanoi, the capital city of Vietnam, to ...understand the status of background contamination, accumulation pattern, sources, and toxic implications for benthic organisms. Total PBDE concentrations in all sediment samples ranged from 0.03 to 17.5 ng/g dry weight (mean 1.33 ng/g dry wt). The most predominant congeners were BDE-47 and BDE-99, which comprised 30 and 25 % of total PBDE concentrations, respectively. Results from statistical analysis indicated that the potential sources of PBDEs of sediments in Hanoi may come from penta-BDE and octa-BDE mixtures. Risk quotients of PBDEs in sediments were also calculated for a benthic species, ranged from 2.12 × 10
−6
− 1.60 × 10
−2
, and were markedly lower than threshold value for occurrence of any ecotoxicological risk. This study provides some of the most comprehensive data on the occurrence of PBDEs in sediments from lake and river systems in Vietnam.
Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use ...in adult intensive care units (ICUs) across Vietnam.
Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08:00 a.m. on the survey day were included.
Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% 855/1012) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 24.4%), Pseudomonas aeruginosa (100/726 13.8%), and Klebsiella pneumoniae (84/726 11.6%), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively).
A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts.
A total of 23 polybrominated diphenyl ether (PBDE) congeners were measured in soil samples collected in areas with no known point source urban/rural/background (U/R/B) sites and in areas with known ...point source brominated flame retardant (BFR)-related industrial sites (F sites) and e-waste recycling sites (E sites) across five Asian countries. The highest PBDE concentrations were found in BFR-related industrial and e-waste recycling sites. The concentrations of PBDEs in U/R/B sites decreased in the following order: urban > rural > background sites. Total PBDE concentrations were dominated by BDE-209, while BDE-17, -85, -138, -191, -204, and -205 were the least abundant compounds. In both urban sites and rural sites, the mean concentrations of total PBDEs (∑23BDEs) in soils decreased in the following order: Japan > China > South Korea > India > Vietnam. The concentrations of PBDEs in soils were comparable with those reported in other studies. Among the three commercial PBDE mixtures, relatively large contributions of commercial penta-BDE were observed in Vietnam, whereas deca-BDE was the dominant form in mixtures contributing from 55.8 ± 2.5 to 100.0 ± 1.2% of the total PBDEs in soils collected from other four countries. Regression analysis suggested that local population density (PD) is a good indicator of PBDEs in soils of each country. Significant and positive correlation between soil organic content and PBDE level was observed in Chinese soil for most nondeca-BDE homologues with their usage stopped 10 years ago, indicating its important role in controlling the revolatilization of PBDEs from soil and changing the spatial trend of PBDE in soil from the primary distribution pattern to the secondary distribution pattern, especially when primary emission is ceased.
There is experimental evidence that the astaxanthin, betanin, and epigallocatechin-3-gallate (EGCG) compounds slow down the aggregation kinetics and the toxicity of the amyloid-β (Aβ) peptide. How ...these inhibitors affect the self-assembly at the atomic level remains elusive. To address this issue, we have performed for each ligand atomistic replica exchange molecular dynamic (REMD) simulations in an explicit solvent of the Aβ11–40 trimer from the U-shape conformation and MD simulations starting from Aβ1–40 dimer and tetramer structures characterized by different intra- and interpeptide conformations. We find that the three ligands have similar binding free energies on small Aβ40 oligomers but very distinct transient binding sites that will affect the aggregation of larger assemblies and fibril elongation of the Aβ40 peptide.
This article presents a novel concept for an Origami-inspired shading device based on dynamic daylight that can be used to improve the daylight performance of a target building and reduce the energy ...consumption for the building. The daylight performance is evaluated based on the Leed v4 (Leadership in Energy and Environmental Design) daylight criterion. The proposed shading device is experimented in an office located in Ho Chi Minh City, Vietnam, where there is a tropical monsoon climate being hot and humid by the year. To investigate the effectiveness of the proposed design in acting as a sun shading system for the office, we consider eight cases corresponding to eight directions which are South, North, East, West, South-East, North-East, South-West, and North-West. An automatic simulation optimization procedure is developed by combining a daylight simulation tool called DIVA and an optimization method called Balancing Composite Motion Optimization (BCMO). BCMO is used to find the optimal design for the proposed kinetic shading device which will help the building to improve daylight performance. It must be noted that the proposed framework is not necessarily tied to any particular optimization tool or type of building. The results show that the proposed kinetic device has outstanding performance as it helps the building to achieve 2, 3 points in Leed v4 for four different directions, including North, North-East, South, North-West.
•An automatic simulation-based optimization approach is investigated through BCMO and DIVA.•Two comparing designs are used to validate the effectiveness of the proposed design.•The proposed kinetic shading device helps building to achieve Leedv4 certification in four directions.•The proposed kinetic shading device could be used as a general sunshade solution in many design situations.•The proposed design could save energy of the building from 25% to 46%.
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