Sulfonamides with Heterocyclic Periphery as Antiviral Agents.

Sulfonamides are the basic motifs for a whole generation of drugs from a large group of antibiotics. Currently, research in the field of the new sulfonamide synthesis has received a "second wind", due to the increase in the synthetic capabilities of organic chemistry and the study of their medical and biological properties of a wide spectrum of biological activity. New reagents and new reactions make it possible to significantly increase the number of compounds with a sulfonamide fragment in combination with other important pharmacophore groups, such as, for example, a wide class of N-containing heterocycles. The result of these synthetic possibilities is the extension of the activity spectrum-along with antibacterial activity, many of them exhibit other types of biological activity. Antiviral activity is also observed in a wide range of sulfonamide derivatives. This review provides examples of the synthesis of sulfonamide compounds with antiviral properties that can be used to develop drugs against coxsackievirus B, enteroviruses, encephalomyocarditis viruses, adenoviruses, human parainfluenza viruses, Ebola virus, Marburg virus, SARS-CoV-2, HIV and others. Since over the past three years, viral infections have become a special problem for public health throughout the world, the development of new broad-spectrum antiviral drugs is an extremely important task for synthetic organic and medicinal chemistry. Sulfonamides can be both sources of nitrogen for building a nitrogen-containing heterocyclic core and the side chain substituents of a biologically active substance. The formation of the sulfonamide group is often achieved by the reaction of the N-nucleophilic center in the substrate molecule with the corresponding sulfonylchloride. Another approach involves the use of sulfonamides as the reagents for building a nitrogen-containing framework.

Metagenomic insights into the effects of benzyl dodecyl dimethyl ammonium bromide (BDAB) shock on bacteria-driven nitrogen removal in a moving-bed biofilm reactor (MBBR).

The use of disinfectants made from quaternary ammonium compounds (QACs) has greatly increased since the outbreak of SARS-CoV-2. However, the effect of QACs on wastewater treatment performance is still unclear. In this study, a commonly used QAC, i.e., benzyl dodecyl dimethyl ammonium bromide (BDAB), was added to a moving-bed biofilm reactor (MBBR) to investigate BDAB's effect on nutrient removal. When the BDAB concentration was increased to 50 mg L-1, the ammonia removal efficiency (ARE) greatly decreased, as did the nitrate production rate constants (NPR). This inhibition was partly recovered by decreasing the BDAB concentration to 30 mg L-1. Metagenomic sequencing revealed the functional genera present during different stages of the control (Rc) and BDAB-added reactors (Re). The enriched genera (Rudaea, Nitrosospira, Sphingomonas, and Rhodanobacter) in Rc mainly related to the nitrogen metabolism, while the enriched genera in Re was BDAB-concentration dependent. Functional genes analysis suggested that a lack of ammonia oxidase-encoding genes (amoABC) may have caused a decrease in ARE in Re, while the efflux pump-encoding genes emrE, mdfA, and oprM and a gene encoding BAC oxygenase (oxyBAC) were responsible for BDAB resistance. The increase in the total abundance of antibiotic resistance genes (ARGs) in Re revealed a potential risk arising from BDAB. Overall, this study revealed the potential effect and ecological risks of BDAB introduction in WWTPs.

A New Complex Design of Fe (II) Isoleucine Dithiocarbamate as a Novel Anticancer and Antivirus against SARSCOV-2 (COVID-19).

BACKGROUND: This study was carried out to synthesize a new complex of Fe(II) with isoleucine dithiocarbamate ligand and to determine its potential as an anticancer and antiviral agent for SARSCOV-2. METHODS: The synthesized complexes were then characterized by UV-vis and FT-IR spectroscopy and their melting points. The value of the conductivity of the complex compound is also determined. Anti-cancer activity was tested in vitro and molecular docking. Its potential as an antiviral against SARSCOV-2 was also carried out by molecular docking. Pharmacokinetics/ADMET properties were also carried out on the complex. RESULT: Spectral results showed the successful synthesis of Fe(II) isoleucine dithiocarbamate complex. The complex produced UV-vis spectra at 268 and 575 nm, and the IR data at 399-599 cm-1 showed the coordination between the Fe(II) atoms with sulphur, nitrogen and oxygen of the isoleucine dithiocarbamate ligand. Fe(II) isoleucine dithiocarbamate had a cytotoxicity effect on the MCF-7 cell line (IC50 =613 µg/mL). The complex significantly caused morphological changes in the breast cancer cell line, finally leading to cell apoptosis. CONCLUSION: Cytotoxic test of Fe(II) isoleucine dithiocarbamate showed moderate anticancer activity on MCF-7 cancer cells and showed antiviral activity against SARSCOV-2 by interfering with spike glycoprotein -ACE2 receptors, and inhibiting major proteases and 3Clpro.

Spatiotemporal trends and impact of Covid-19 lockdown on eight sewage contaminants in Brisbane, Australia, from 2012 to 2020.

This study aims to investigate the spatiotemporal trends and impact of COVID-19 lockdowns to the profile of physiochemical parameters in the influent of wastewater treatment plants (WWTPs) around Brisbane, Australia. One 24-hr composite influent sample was collected from 10 WWTPs and analyzed for a range of physiochemical parameters per week (i.e., chemical oxygen demand (COD), total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), ammonia, volatile suspended solid (VSS)) and per month (i.e., Ni and Cr) from 2012 to 2020, including the period of COVID-19 lockdowns in the region. The catchments studied were urban, with a mix of domestic and industrial activities contributing towards the contaminant profile. Statistical analysis identified that industrial and commercial land use, as well as population size had a large impact to the parameter loads and profile. Per capita mass loads of Cr in one catchment were 100 times higher than in others from one industrial point source. TP demonstrated a potential monotonic decrease over time due to practical reduction policies that have been implemented for phosphorous content in household detergents, except for one catchment where trade waste from food manufacturing industries contributed to an overall increase of 6.9%/year TP. The COVID-19 lockdown (March-April 2020) posed different impact on different catchments, either decrease (7-61%) or increase (2-40%) of most parameter loads (e.g., COD, TOC, TN, TP, VSS, Ammonia), which was likely driven by catchment characteristics (i.e., the proportion of residential, commercial, and industrial land uses). This study enhances our understanding of spatiotemporal trend of contaminants in the catchments for further effective source control.

Ultrasensitive FRET-based aptasensor for interleukin-6 as a biomarker for COVID-19 progression using nitrogen-doped carbon quantum dots and gold nanoparticles.

A label-free and specific FRET-based interleukin-6 (IL-6) aptasensor was developed using a DNA aptamer modified with nitrogen-doped carbon quantum dots (NCDs) and gold nanoparticles (AuNPs) as a donor-quencher pair. The assayed target was capable of disrupting the donor-acceptor assemblies yielding a concentration-related fluorescence recovery of NCDs (λem = 445 nm and λex = 350 nm). By designing two different probes, the interaction of DNA aptamers with IL-6 protein was studied using FRET efficiency. It appeared that the sensing probes showed slightly different sensing profiles. One of the aptasensors showed a linear response of 1.5-5.9 pg/mL for IL-6 with a coefficient of determination of R2 ≥ 0.99 and the a detection limit of 0.82 pg/mL (at S/N = 3). The experimental results indicated that the biosensor can be applied to determine IL-6 in human serum (with recovery of 95.7-102.9%). Due to the high sensitivity, excellent selectivity, and simplicity of the procedure, this strategy represents a promising alternative for IL-6 sensing in clinical applications.

Acute stress of the typical disinfectant glutaraldehyde-didecyldimethylammonium bromide (GD) on sludge microecology in livestock wastewater treatment plants: Effect and its mechanisms.

Glutaraldehyde and didecyldimethylammonium bromide (GD) is a disinfectant widely used to prevent African swine fever (ASF) in livestock farms. However, the effect of residual GD on the activated sludge microbial ecology of receiving wastewater treatment plants (WWTPs) remains largely unknown. In this study, seven simulated systems were established to research the effects of GD on WWTPs and reveal the underlying mechanisms of microecological responses to GD at different concentrations. Both the nitrogen and carbon removal rates decreased with increasing GD concentrations, and nitrogen metabolism was inhibited more obviously, but the inhibition weakened with increasing stress duration. Microorganisms activated their SoxRS systems to promote ATP synthesis and electron transfer to support the hydrolysis and efflux of GD by producing a small number of ROS when exposed to GD at less than 1 mg/L. The overproduction of ROS led to a decrease of antioxidant and nitrogen removal enzyme activities, and upregulation of the porin gene increased the risk of GD entering the intracellular space upon exposure to GD at concentrations higher than 1 mg/L. Some denitrifiers survived via resistance and their basic capabilities of sugar metabolism and nitrogen assimilation. Notably, low concentrations of disinfectants could promote vertical and horizontal transfer of multiple resistance genes, especially aminoglycosides, among microorganisms, which might increase not only the adaptation capability of denitrifiers but also the risk to ecological systems. Therefore, the risks of disinfectants targeting ASF on ecology and health as well as the effects of disinfectant residuals from the COVID-19 epidemic should receive more attention.

COVID-19 lockdown-driven changes in the Ganga River ecosystem in response to human perturbations.

We examined 10 subsurface water, 5 benthic water and 19 sediment (02 cm) samples along a 518 km of the middle segment of the Ganga River to assess the possible improvements that resulted from the industrial shutdown during the COVID-19 pandemic. The sites included the main stem river, tributary confluences, and two point sources, one of which releases metal-rich effluents and the other flushes municipal sewage. We found significant declines in the carbon, nutrient and metal concentrations in both the water and sediment. Even the most polluted zones did not show hypoxia (dissolve oxygen; DO < 2.0 mg L-1) that had been observed in the previous year. Despite a significant decline in carbon and nitrogen as substrates, the activities of extracellular enzymes (EEs), such as ß-D-glucosidase, FDAase and protease in sediment (0-2 cm depth), increased significantly (p < 0.05) in response to the declining metal concentrations resulting from the industrial shutdown. We found strong negative correlations between EE activity and the concentrations of metal pollutants measured in 2019, but the correlations between these variables appeared poor in 2020 (lockdown period). Also, we found large variances (low stability coefficients) during the period of strong anthropogenic effects (2019). The study indicates that industrial sources are important contributors of metal pollution in the Ganga River and has relevance exploring river ecosystem recovery windows for management decisions.

Hydrothermal deconstruction of single-use personal protective equipment during the COVID-19 pandemic.

To minimise the transmission of the SARS-CoV-2 virus, there has been a substantial increase in the production and usage of synthetic personal protective equipment (PPE) globally. Consequently, single-use PPE have been widely adopted without appropriate regulations for their disposal, leading to extensive environmental contamination worldwide. This study investigates the non-catalytic hydrothermal deconstruction of different PPE items, including isolation gowns, gloves, goggles, face shields, surgical masks, and filtering-facepiece respirators. The selected PPE items were subjected to hydrothermal deconstruction for 90 min in the presence of 30-bar initial oxygen pressure, at temperatures ranging between 250 °C and 350 °C. The solid content in form of total suspended solids (TSS) was reduced up to 97.6%. The total chemical oxygen demand (tCOD) and soluble chemical oxygen demand (sCOD) decreased with increasing deconstruction temperature, and at 350 °C the lowest tCOD and sCOD content of 546.6 mg/L and 470 mg/L, respectively, was achieved. Short-chained volatile fatty acids were produced after 90 min of deconstruction, predominantly acetic acid at concentrations up to 8974 mg/L. Ammonia nitrogen content (NH3-N) of up to 542.6 mg/L was also detected. Carbon dioxide (CO2) and unreacted oxygen (O2) were the main gaseous by-products at up to 15.6% (w/w) and 88.7% (w/w), respectively. The findings suggest that non-catalytic hydrothermal deconstruction is a viable option to process and manage PPE waste.

Wild type and variants of SARS-COV-2 in Parisian sewage: presence in raw water and through processes in wastewater treatment plants.

The presence of SARS-CoV-2 RNA has been extensively reported at the influent of wastewater treatment plants (WWTPs) worldwide, and its monitoring has been proposed as a potential surveillance tool to early alert of epidemic outbreaks. However, the fate of the SARS-CoV-2 RNA in the treatment process of WWTP has not been widely studied yet; therefore, in this study, we aimed to evaluate the efficiency of treatment processes in reducing SARS-CoV-2 RNA levels in wastewater. The treatment process of three WWTPs of the Parisian area in France was monitored on six different weeks over a period of 2 months (from April 14 to June 9, 2021). SARS-CoV-2 RNA copies were detected using digital polymerase chain reaction (dPCR). Investigation on the presence of variants of concern (Del69-70, E484K, and L452R) was also performed. Additionally, SARS-CoV-2 RNA loads in the WWTPs influents were expressed as the viral concentration in per population equivalent (PE) and showed a good correlation with French public health indicators (incidence rate). SARS-CoV-2 RNA loads were notably reduced along the water treatment lines of the three WWTPs studied (2.5-3.4 log reduction). Finally, very low SARS-CoV-2 RNA loads were detected in effluents (non-detected in over half of the samples) which indicated that the potential risk of the release of wastewater effluents to the environment is probably insignificant, in the case of WWTPs enabling an efficient biological removal of nitrogen.

Implication of cell culture methods and biases on UV inactivation of viruses.

Inactivation of human respiratory viruses in air and on surfaces is important to control their spread. Exposure to germicidal ultraviolet (UV-C) light damages viral nucleic acid rendering them non-infectious. Most of the recent viral inactivation studies have not considered potential artifacts caused by interactions between UV-C light and culture media used to suspend and deposit virus on surfaces. We show that the reactive oxygen and nitrogen species (ROS and RNS) form when commonly used virus culture media is exposed to 265 nm irradiation from light emitting diodes (LEDs) at UV-C doses (4 or 40 mJ/cm2) commonly considered to achieve multiple log-inactivation of virus. Surface viral inactivation values were enhanced from 0.49 to 2.92 log10 of viruses in DMEM, EMEM or EMEM-F as compared to absence of culture media (only suspended in Tris-buffer). The mechanisms responsible for the enhanced surface inactivate is hypothesized to involve photo-activation of vitamins and dyes present in the culture media, deposited with the virus on surfaces to be disinfected, which produce ROS and RNS. Given the rapidly growing research and commercial markets for UV-C disinfecting devices, there is a need to establish surface disinfecting protocols that avoid viral inactivation enhancement artifacts associated with selection and use of common cell culture media in the presence of UV-C light. This study addresses this weak link in the literature and highlights that inadequate selection of virus suspension media may cause a bias (i.e., over-estimation) for the UV-C dosages required for virus inactivation on surfaces.

Association of nitrogen balance trajectories with clinical outcomes in critically ill COVID-19 patients: A retrospective cohort study.

BACKGROUND & AIMS: The intensity and duration of the catabolic phase in COVID-19 patients can differ between survivors and non-survivors. The purpose of the study was to assess the determinants of, and association between, nitrogen balance trajectories and outcome in critically ill COVID-19 patients. METHODS: This retrospective monocentric observational study involved patients admitted to the intensive care unit (ICU) of the University Hospital of Clermont Ferrand, France, from January 2020 to May 2021 for COVID-19 pneumonia. Patients were excluded if referred from another ICU, if their ICU length of stay was <72 h, or if they were treated with renal replacement therapy during the first seven days after ICU admission. Data were collected prospectively at admission and during ICU stay. Death was recorded at the end of ICU stay. Comparisons of the time course of nitrogen balance according to outcome were analyzed using two-way ANOVA. At days 3, 5, 7, 10 and 14, uni- and multivariate logistic regression analyses were performed to assess the impact of a non-negative nitrogen-balance on ICU death. To investigate the relationships between nitrogen balance, inflammatory markers and protein intake, linear and non-nonlinear models were run at days 3, 5 and 7, and the amount of protein intake necessary to reach a neutral nitrogen balance was calculated. Subgroup analyses were carried out according to BMI, age, and sex. RESULTS: 99 patients were included. At day 3, a similar negative nitrogen balance was observed in survivors and non-survivors: -16.4 g/d [-26.5, -3.3] and -17.3 g/d [-22.2, -3.8] (p = 0.54). The trajectories of nitrogen balance over time thus differed between survivors and non-survivors (p = 0.01). In survivors, nitrogen balance increased over time, but decreased from day 2 to day 6 in non-survivors, and thereafter increased slowly up to day 14. At days 5 and 7, a non-negative nitrogen-balance was protective from death. Administering higher protein amounts was associated with higher nitrogen balance. CONCLUSION: We report a prolonged catabolic state in COVID patients that seemed more pronounced in non-survivors than in survivors. Our study underlines the need for monitoring urinary nitrogen excretion to guide the amount of protein intake required by COVID-19 patients.

Surveillance of SARS-CoV-2 in nine neighborhood sewersheds in Detroit Tri-County area, United States: Assessing per capita SARS-CoV-2 estimations and COVID-19 incidence.

Wastewater-based epidemiology (WBE) has been suggested as a useful tool to predict the emergence and investigate the extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we screened appropriate population biomarkers for wastewater SARS-CoV-2 normalization and compared the normalized SARS-CoV-2 values across locations with different demographic characteristics in southeastern Michigan. Wastewater samples were collected between December 2020 and October 2021 from nine neighborhood sewersheds in the Detroit Tri-County area. Using reverse transcriptase droplet digital polymerase chain reaction (RT-ddPCR), concentrations of N1 and N2 genes in the studied sites were quantified, with N1 values ranging from 1.92 × 102 genomic copies/L to 6.87 × 103 gc/L and N2 values ranging from 1.91 × 102 gc/L to 6.45 × 103 gc/L. The strongest correlations were observed with between cumulative COVID-19 cases per capita (referred as COVID-19 incidences thereafter), and SARS-CoV-2 concentrations normalized by total Kjeldahl nitrogen (TKN), creatinine, 5-hydroxyindoleacetic acid (5-HIAA) and xanthine when correlating the per capita SARS-CoV-2 and COVID-19 incidences. When SARS-CoV-2 concentrations in wastewater were normalized and compared with COVID-19 incidences, the differences between neighborhoods of varying demographics were reduced as compared to differences observed when comparing non-normalized SARS-CoV-2 with COVID-19 cases. This indicates when studying the disease burden in communities of different demographics, accurate per capita estimation is of great importance. The study suggests that monitoring selected water quality parameters or biomarkers, along with RNA concentrations in wastewater, will allow adequate data normalization for spatial comparisons, especially in areas where detailed sanitary sewage flows and contributing populations in the catchment areas are not available. This opens the possibility of using WBE to assess community infections in rural areas or the developing world where the contributing population of a sample could be unknown.

Toxicity and virucidal activity of a neon-driven micro plasma jet on eukaryotic cells and a coronavirus.

Plasma medicine is a developing field that utilizes the effects of cold physical plasma on biological substrates for therapeutic purposes. Approved plasma technology is frequently used in clinics to treat chronic wounds and skin infections. One mode of action responsible for beneficial effects in patients is the potent antimicrobial activity of cold plasma systems, which is linked to their unique generation of a plethora of reactive oxygen and nitrogen species (ROS). During the SARS-CoV-2 pandemic, it became increasingly clear that societies need novel ways of passive and active protection from viral airway infections. Plasma technology may be suitable for superficial virus inactivation. Employing an optimized neon-driven micro plasma jet, treatment time-dependent ROS production and cytotoxic effects to different degrees were found in four different human cell lines with respect to their metabolic activity and viability. Using the murine hepatitis virus (MHV), a taxonomic relative of human coronaviruses, plasma exposure drastically reduced the number of infected murine fibroblasts by up to 3000-fold. Direct plasma contact (conductive) with the target maximized ROS production, cytotoxicity, and antiviral activity compared to non-conductive treatment with the remote gas phase only. Strikingly, antioxidant pretreatment reduced but not abrogated conductive plasma exposure effects, pointing to potential non-ROS-related mechanisms of antiviral activity. In summary, an optimized micro plasma jet showed antiviral activity and cytotoxicity in human cells, which was in part ROS-dependent. Further studies using more complex tissue models are needed to identify a safe dose-effect window of antiviral activity at modest toxicity.

Mask disinfection using atmospheric pressure cold plasma.

OBJECTIVES: Mask usage has increased over the last few years due to the COVID-19 pandemic, resulting in a mask shortage. Furthermore, their prolonged use causes skin problems related to bacterial overgrowth. To overcome these problems, atmospheric pressure cold plasma was studied as an alternative technology for mask disinfection. METHODS: Different microorganisms (Pseudomonas aeruginosa, Escherichia coli, Staphylococcus spp.), different gases (nitrogen, argon, and air), plasma power (90-300 W), and treatment times (45 seconds to 5 minutes) were tested. RESULTS: The best atmospheric pressure cold plasma treatment was the one generated by nitrogen gas at 300 W and 1.5 minutes. Testing of breathing and filtering performance and microscopic and visual analysis after one and five plasma treatment cycles, highlighted that these treatments did not affect the morphology or functional capacity of the masks. CONCLUSION: Considering the above, we strongly believe that atmospheric pressure cold plasma could be an inexpensive, eco-friendly, and sustainable mask disinfection technology enabling their reusability and solving mask shortage.

Cold Atmospheric Plasma Ameliorates Skin Diseases Involving Reactive Oxygen/Nitrogen Species-Mediated Functions.

Skin diseases are mainly divided into infectious diseases, non-infectious inflammatory diseases, cancers, and wounds. The pathogenesis might include microbial infections, autoimmune responses, aberrant cellular proliferation or differentiation, and the overproduction of inflammatory factors. The traditional therapies for skin diseases, such as oral or topical drugs, have still been unsatisfactory, partly due to systematic side effects and reappearance. Cold atmospheric plasma (CAP), as an innovative and non-invasive therapeutic approach, has demonstrated its safe and effective functions in dermatology. With its generation of reactive oxygen species and reactive nitrogen species, CAP exhibits significant efficacies in inhibiting bacterial, viral, and fungal infections, facilitating wound healing, restraining the proliferation of cancers, and ameliorating psoriatic or vitiligous lesions. This review summarizes recent advances in CAP therapies for various skin diseases and implicates future strategies for increasing effectiveness or broadening clinical indications.

Dissolved organic nitrogen derived from wastewater denitrification: Composition and nitrogenous disinfection byproduct formation.

Microbially derived dissolved organic nitrogen (mDON) is a major fraction of effluent total nitrogen at wastewater treatment plants with enhanced nutrient removal, which stimulates phytoplankton blooms and formation of toxic nitrogenous disinfection by-products (N-DBPs). This study identified denitrifiers as major contributors to mDON synthesis, and further revealed the molecular composition, influential factors and synthetic microorganisms of denitrification-derived mDON compounds leading to N-DBP formation. The maximum mDON accumulated during denitrification was 8.92% of converted inorganic nitrogen, higher than that of anammox (4.24%) and nitrification (2.76%). Sodium acetate addition at relatively high C/N ratio (5-7) favored mDON formation, compared with methanol and low C/N (1-3). Different from acetate, methanol-facilitated denitrification produced 13-69% more lignin-like compounds than proteins using Orbitrap LC-MS. The most abundant N-DBPs formed from denitrification-derived mDON were N-nitrosodibutylamine and dichloroacetonitrile (13.32 µg/mg mDON and 12.21 µg/mg mDON, respectively). Major amino acids, aspartate, glycine, and alanine were positively correlated with typical N-DBPs. Biosynthesis and degradation pathways of these N-DBP precursors were enriched in denitrifiers belonging to Rhodocyclaceae, Mycobacteriaceae and Hyphomicrobiaceae. As intensive disinfection is applied at worldwide wastewater treatment plants during COVID-19, carbon source facilitated denitrification should be better managed to reduce both effluent inorganic nitrogen and DON, mitigating DON and N-DBP associated ecological risks in receiving waters.

Ammonia Emissions from NPK Fertilizer Production Plants: Emission Characteristics and Emission Factor Estimation.

Fertilizers are made from manure, but they are also produced through chemical processes. Fertilizer is an ammonia emission source; it releases ammonia when used. Ammonia is also emitted during the production process. Although many studies related to fertilizer application have been conducted, there are few research cases related to the production process and related emissions are not calculated. In this study, the ammonia emissions from NPK (nitrogen phosphorus Potassium oxide) fertilizer production facilities were checked through actual measurement and related characteristics were analyzed. In addition, emission factors were developed, and the necessity of developing emission factors was also confirmed. As a result of the development of the emission factor, it was found to be 0.001 kgNH3/ton, which is like the range of emission factors in related fields. The NPK ammonia emission factor of this study was found to be higher than the minimum emission factor currently applied in South Korea, and it was judged to be a level that can be used as an emission factor.

Basic influent sewage quality reflects sewershed characteristics in Tokyo city.

Sewage comprises multifarious information on sewershed characteristics. For instance, influent sewage quality parameters (ISQPs) (e.g., total nitrogen (TN)) are being monitored regularly at all treatment plants. However, the relationship between ISQPs and sewershed characteristics is rarely investigated. Therefore, this study statistically investigated relationships between ISQPs and sewershed characteristics, covering demographic, social, and economic properties in Tokyo city as an example of a megacity. To this end, we collected ISQPs and sewershed characteristic data from 2015 to 2020 in 10 sewersheds in Tokyo city. By principal component analysis, spatial variability of ISQPs was aggregated into two principal components (89.8% contribution in total), indicating organics/nutrients and inorganic salts, respectively. Concentrations of organics/nutrients were significantly correlated with the population in sewersheds (daytime population density, family size, age distribution, etc.). Inorganic salts are significantly correlated with land cover ratios. Finally, a multiple regression model was developed for estimating the concentration of TN based on sewershed characteristics (R2=0.97). Scenario analysis using the regression model revealed that possible population movements in response to the coronavirus pandemic would substantially reduce the concentration of TN. These results indicate close relationships between ISQPs and sewershed characteristics and the potential applicability of big data of ISQPs to estimate sewershed characteristics and vice versa.

Development of Azaindole-Based Frameworks as Potential Antiviral Agents and Their Future Perspectives.

The azaindole (AI) framework continues to play a significant role in the design of new antiviral agents. Modulating the position and isosteric replacement of the nitrogen atom of AI analogs notably influences the intrinsic physicochemical properties of lead compounds. The intra- and intermolecular interactions of AI derivatives with host receptors or viral proteins can also be fine tuned by carefully placing the nitrogen atom in the heterocyclic core. This wide-ranging perspective article focuses on AIs that have considerable utility in drug discovery programs against RNA viruses. The inhibition of influenza A, human immunodeficiency, respiratory syncytial, neurotropic alpha, dengue, ebola, and hepatitis C viruses by AI analogs is extensively reviewed to assess their plausible future potential in antiviral drug discovery. The binding interaction of AIs with the target protein is examined to derive a structural basis for designing new antiviral agents.

Synthesis and Applications of Nitrogen-Containing Heterocycles as Antiviral Agents.

Viruses have been a long-term source of infectious diseases that can lead to large-scale infections and massive deaths. Especially with the recent highly contagious coronavirus (COVID-19), antiviral drugs were developed nonstop to deal with the emergence of new viruses and subject to drug resistance. Nitrogen-containing heterocycles have compatible structures and properties with exceptional biological activity for the drug design of antiviral agents. They provided a broad spectrum of interference against viral infection at various stages, from blocking early viral entry to disrupting the viral genome replication process by targeting different enzymes and proteins of viruses. This review focused on the synthesis and application of antiviral agents derived from various nitrogen-containing heterocycles, such as indole, pyrrole, pyrimidine, pyrazole, and quinoline, within the last ten years. The synthesized scaffolds target HIV, HCV/HBV, VZV/HSV, SARS-CoV, COVID-19, and influenza viruses.