ABSTRACT
Dengue fever (DF) is an endemic disease that has become a public health concern around the globe. The NS3 protease-helicase enzyme is an important target for the development of antiviral drugs against DENV (dengue virus) due to its impact on viral replication. Inhibition of the activity of the NS3 protease-helicase enzyme complex significantly inhibits the infection associated with DENV. Unfortunately, there are no scientifically approved antiviral drugs for its prevention. However, this study has been developed to find natural bioactive molecules that can block the activity of the NS3 protease-helicase enzyme complex associated with DENV infection through molecular docking, MM-GBSA (molecular mechanics-generalized born surface area), and molecular dynamics (MD) simulations. Three hundred forty-two (342) compounds selected from twenty traditional medicinal plants were retrieved and screened against the NS3 protease-helicase protein by molecular docking and MM-GBSA studies, where the top six phytochemicals have been identified based on binding affinities. The six compounds were then subjected to pharmacokinetics and toxicity analysis, and we conducted molecular dynamics simulations on three protein-ligand complexes to validate their stability. Through computational analysis, this study revealed the potential of the two selected natural bioactive inhibitors (CID-440015 and CID-7424) as novel anti-dengue agents.
ABSTRACT
Tannery sludge, heavy metals (HMs) enriched hazardous solid waste, is produced extensively in many regions of the world. Even though the sludge is hazardous, it can be considered a material resource, if organic matter and HMs in the sludge can be stabilized to minimize its negative environmental impacts. This research aimed to evaluate the efficacy of using subcritical water (SCW) treatment for tannery sludge treatment through immobilization and thus reduction of HMs to mitigate their potential environmental risk and toxicity. HMs in the tannery sludge were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and the average concentration of HMs (mg kg-1) was found in the following decreasing order of Cr (12 950) > Fe (1265) > Cu (76) > Mn (44) > Zn (36) > Pb (14) with very high Cr concentration. The result of toxicity characteristics leaching procedure and sequential extraction procedure tests revealed that the raw tannery sludge leachate contained 11.24 mg L-1 Cr, which classified the raw tannery sludge into a very high-risk category. After SCW treatment, the concentration of Cr in leachate was reduced to 1.6 mg L-1 indicating risk reduction to a low-risk category. The eco-toxicity levels of other HMs also decreased considerably after SCW treatment. X-ray diffractometry (XRD) and scanning electron microscopy (SEM) analysis were employed to identify the effective immobilizing substances formed in the SCW treatment process. The favorable formation of immobilizing orthorhombic tobermorite (Ca5Si6O16(OH)2·4H2O) at 240 °C in the SCW treatment process was confirmed by XRD and SEM analysis. The results confirmed that the formation of 11 Å tobermorite is capable of strongly immobilizing HMs in the SCW treatment process. Further, both orthorhombic 11 Å tobermorite and 9 Å tobermorite were successfully synthesized by SCW treatment on a mixture of tannery sludge including rice husk silica and Ca(OH)2 with water under rather mild conditions. Hence, it can be concluded that SCW treatment of tannery sludge with supplementary silica from rice husk can effectively immobilize the HMs and significantly reduce their environmental risk through tobermorite formation.
ABSTRACT
Road dust, which reflects ambient air quality, receives various pollutants including toxic metal(oid)s from several natural and/or anthropogenic sources. This manuscript reports a comprehensive evaluation of the levels of seventeen metal(oid)s in road dust of a megacity (Dhaka, Bangladesh). Different evaluation approaches were implemented including statistical analysis and GIS mapping, besides environmental, ecological, and human health risk indices. From 30 sampling sites, representative samples were collected, which were analyzed by neutron activation analysis. The average concentrations (± SD) of Na, Mg, Al, Sc, Ti, V, Cr, Mn, Fe, Co, Zn, As, Rb, Sb, Cs, Ba, and W were 11,738 ± 560 µg g-1, 12,410 ± 1249 µg g-1, 62,127 ± 5937 µg g-1, 8.89 ± 0.47 µg g-1, 5224 ± 1244 µg g-1, 66 ± 8 µg g-1, 66.7 ± 6.9 µg g-1, 547 ± 110 µg g-1, 25,150 ± 1723 µg g-1, 8.39 ± 0.65 µg g-1, 125 ± 17 µg g-1, 3.63 ± 0.56 µg g-1, 87 ± 9 µg g-1, 0.75 ± 0.28 µg g-1, 4.40 ± 0.48 µg g-1, 397 ± 87 µg g-1, and 3.82 ± 1.77 µg g-1, respectively. The distance-based redundancy analysis showed that the northern region was enriched with Na, Mn, Al, Fe, Zn, and Rb, while the southern region was enriched with Fe, Al, Ti, Cr, and Mg. The GIS mapping shows hot spots of Sc, Cr, Zn, and Cs were observed mostly in heavy traffic areas. Significant positive correlations of Fe-Sc, Al-Mg, V-Mg, V-Al, Cs-Rb, Cs-Sc, Rb-Sc, As-Na, and Cs-Rb invoked their inter-dependency and persistence in road dust. Depending on a set of environmental and ecological index-based calculation, the degree of metal(oid) pollution followed the descending order as W > Sb > Zn > Cr > As > Ti > Sc > V, while no pollution was recorded by Mn, Fe, Al, Rb, Cs, Co, and Ba. Importantly, the total hazard index values for adults and children were higher than unity, indicating potential non-carcinogenic health risks from exposure of road dust. Furthermore, the total carcinogenic risks from Cr and As through ingestion and dermal contact exceeded the standard guideline values. The implementation of different evaluation approaches strengthens the findings of metal(oid) source apportionment.
