Structures of Two Human Astrovirus Capsid/Neutralizing Antibody Complexes Reveal Distinct Epitopes and Inhibition of Virus Attachment to Cells.

Human astrovirus is an important cause of viral gastroenteritis worldwide. Young children, the elderly, and the immunocompromised are especially at risk for contracting severe disease. However, no vaccines exist to combat human astrovirus infection. Evidence points to the importance of antibodies in protecting healthy adults from reinfection. To develop an effective subunit vaccine that broadly protects against diverse astrovirus serotypes, we must understand how neutralizing antibodies target the capsid surface at the molecular level. Here, we report the structures of the human astrovirus capsid spike domain bound to two neutralizing monoclonal antibodies. These antibodies bind two distinct conformational epitopes on the spike surface. We add to existing evidence that the human astrovirus capsid spike contains a receptor-binding domain and demonstrate that both antibodies neutralize human astrovirus by blocking virus attachment to host cells. We identify patches of conserved amino acids which overlap or border the antibody epitopes and may constitute a receptor-binding site. Our findings provide a basis for developing therapies to prevent and treat human astrovirus gastroenteritis. IMPORTANCE Human astroviruses infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies block astrovirus infection. Here, we determined the crystal structures of the astrovirus capsid protein in complex with two virus-neutralizing antibodies. We show that the antibodies bind to two distinct sites on the capsid spike domain, however, both antibodies block virus attachment to human cells. Importantly, our findings support the use of the human astrovirus capsid spike as an antigen in a subunit-based vaccine to prevent astrovirus disease.

Mechanism and Origin of Remote Stereocontrol in the Organocatalytic Enantioselective Formal C(sp2)-H Alkylation Using Nitroalkanes as Alkylating Agents.

Experimental 13C kinetic isotope effects (KIEs) and density functional theory (DFT) calculations are used to evaluate the mechanism and origin of enantioselectivity in the formal C(sp2)-H alkylative desymmetrization of cyclopentene-1,3-diones using nitroalkanes as the alkylating agent. An unusual combination of an inverse (∼0.980) and a normal (∼1.033) KIE is observed on the bond-forming carbon atoms of the cyclopentene-1,3-dione and nitroalkane, respectively. These data provide strong support for a mechanism involving reversible carbon-carbon bond formation followed by rate- and enantioselectivity-determining nitro group elimination. The theoretical free-energy profile and the predicted KIEs indicate that this elimination event occurs via an E1cB pathway. The origin of remote stereocontrol is evaluated by distortion-interaction and SAPT0 analyses of the E1cB transition states leading to both enantiomers.

Buckeye Rot of Tomato in India: Present Status, Challenges, and Future Research Perspectives.

Tomato in India is commonly exposed to various diseases of fungal, bacterial, and viral origin, resulting in substantial yield losses (≥50%). Buckeye rot (caused by Phytophthora nicotianae var. parasitica) is among the major constraints in the successful cultivation of tomato crops in various parts of the world, including the Solan district of Himachal Pradesh state, India. The fruit rot becomes more devastating under high humidity and wet soils. Symptoms generally appear on green fruit as alternate dark- and light-brown concentric rings. The genome size of P. nicotianae var. parasitica is 82 Mb with >23,000 predicted genes. High humidity (>60%) and optimal temperatures (20 to 25°C), along with rainfall (≥10 mm), help to disperse the pathogen because the inoculum reaches the fruit through splashing rain. Sporangia germinate indirectly by producing zoospores at 20 to 25°C or directly via germ tubes at >25°C. In the absence of suitable resistant varieties, no single management practice is sufficient to keep the disease below the economic threshold level; therefore, integration of cultural and chemical methods is preferable. This article aims to focus on the etiology and management challenges of buckeye rot. We recommend innovative disease management strategies such as identification and deployment of resistant cultivars as well as spraying of synthetic chemical fungicides, biocontrol agents, and use of abiotic chemicals that induce resistance for developing sustainable crop production practices.

Provenances, preponderances, and distribution of humic acids and organic pollutants in hydro-geosphere: The co-existence, interaction and isotopic biomarkers in the riverine ecosystem.

This paper aims to critically review the importance of geochemical fingerprinting and tracing using biomarkers and stable isotopes in the riverine ecosystem and depicts that isotopic ratios of δ13C, δ15N, and δ34S can be used for tracing pollution sources. Stable isotopes like carbon, hydrogen, nitrogen, oxygen, and sulfur are being used for this purpose, and their isotopic signatures are primarily used to distinguish close sources of organic matter through dual isotopes. The present review is articulated to bridge the critical research gaps of the previous and contemporary documented literature on the genesis and transport of OM between freshwater and marine systems. This review comprehensively provides methods and techniques in geochemical tracing and discusses the future directions to address the challenges of the current methods to enhance the knowledge about the source identification of organic matter in the riverine environment. Tracer geochemistry emphasizes the implications of elemental abundances and isotope ratio variations in geologic substances to track natural earth processes, anthropogenic contaminants, and geochemical signatures in the hydrologic system. The principal constituent of organic matter comprises humic substances like humic acid, fulvic acid, and humin, and these comprise 50-75% of the sediments and DOC in natural waters. Their structural and functional characterization is required to elucidate the transport and fate of organic matter, which are often influenced by several paleoenvironmental factors.

Iridium-Catalyzed Enantioselective and Chemodivergent Allenylic Alkylation of Vinyl Azides for the Synthesis of α-Allenylic Amides and Ketones.

The first enantioselective synthesis of α-allenylic amides and ketones through allenylic alkylation of vinyl azides is reported. In these chemodivergent reactions, cooperatively catalyzed by a IrI /(phosphoramidite,olefin) complex and Sc(OTf)3 , vinyl azides act as the surrogate for both amide enolates and ketone enolates. The desiccant (molecular sieves) plays a crucial role in controlling the chemodivergency of this enantioconvergent and regioselective reaction: Under otherwise identical reaction conditions, the presence of the desiccant led to α-allenylic amides, while its absence resulted in α-allenylic ketones. Utilizing racemic allenylic alcohols as the alkylating agent, the overall process represents a dynamic kinetic asymmetric transformation (DyKAT), where both the products are formed with the same absolute configuration. To the best of our knowledge, this is the first example of the use of vinyl azide as the ketone enolate surrogate in an enantioselective transformation.

Enantioselective Total Synthesis of [3]-Ladderanol through Late-Stage Organocatalytic Desymmetrization.

Ladderane phospholipids, with their unusual ladder-like arrangement of concatenated cyclobutane rings, represent an architecturally unique class of natural products. However, despite their fascinating structure and other necessary impetus, only a few synthetic studies of these molecules have been reported so far. We have now devised a concise total synthesis of [3]-ladderanol, a component of natural ladderane phospholipids, using an organocatalytic enantioselective desymmetrizing formal C(sp2 )-H alkylation. Our synthetic strategy rests on the late-stage introduction of chirality, thus allowing facile access to both enantiomers of [3]-ladderanol as well as an analogue. This is the first time a desymmetrization strategy is applied to the synthesis of [3]-ladderanol. The scope of this desymmetrizing C(sp2 )-H alkylation of meso-cyclobutane-fused cyclohexenediones is also presented.

Catalytic Enantioselective de novo Construction of Chiral Arenes through Desymmetrizing Oxidative [4+2]-Cycloaddition.

Central chirality in arene derivatives arising out of unsymmetrically substituted arene ring is a fascinating yet rarely explored research topic. Here, we report a desymmetrization approach to centrally chiral unfunctionalized arenes, which is enabled by the enantioselective de novo construction of the arene ring. This operationally simple protocol is based on a [4+2]-cycloaddition between polycyclic meso-cyclohexenediones and α,ß-unsaturated aldehydes, and doesn't usually require any external oxidant. Catalyzed by a diphenylprolinol silyl ether, this reaction proceeds via dienamine intermediate and greatly simplifies the access to diversely substituted chiral arenes with outstanding enantioselectivities.

Biopurification of dairy farm wastewater through hybrid constructed wetland system: Groundwater quality and health implications.

Groundwater is under heavily threat owing to enormous infilteration of dairy farm originated wastewater into it. The anoxic environment in the groundwater due to mixing of organic rich wastewater can produce significant alterations in the groundwater quality. It is therefore necessary to treat such wastewaters before discharging to surrounding areas. Therefore, in this study we evaluated a hybrid constructed wetland (CW) system(40 m2 area) consisting of three beds, i.e. Vertical (16 m2) - Horizontal (18 m2) - Vertical (6 m2) connected in series for the treatment of dairy farm wastewater under typical high humid climate in northern India. Tropical perennial plant such as Arundo donax L. was grown on both vertical beds, whereas Hibiscus esculentus L. and Solanum melongena L. were grown on the horizontal bed of the system.The average purification of TSS, BOD3, total N, and P was significant (p < 0.05) in HF bed and recorded as 92.2 ± 6.1, 95 ± 3.8, 83.6 ± 9.0 and 86.1 ± 10.0% respectively.The average load of BOD3, total N, and P in the influent and effluent was recorded (with no significant differences, p > 0.05) as 7.0 ± 7.17, 1.9 ± 0.7, 0.72 ± 0.5 g m-2 day-1and 0.3 ± 0.2, 0.3 ± 0.2 and 0.04 ± 0.01 g m-2 day-1 respectively.The average values of total biomass content of Arundo donax L. were differed significantly and recorded as 0.31 ± 0.06, 0.43 ± 0.17, and 0.43 ± 0.16 g g-1 fresh wt. in control, VF-1, and VF-2 respectively. Therefore, the hybrid CW system can be efficiently used for the treatment of dairy farm wastewater with implications on groundwater and health. Future research may focus on performance analysis of upgraded combined anaerobic reactor and hybrid CW system planted with series of macrophytes for on-site treatment of high strength dairy farm wastewater in tropical regions.

Performance evaluation of crop residue and kitchen waste-derived biochar for eco-efficient removal of arsenic from soils of the Indo-Gangetic plain: A step towards sustainable pollution management.

Biochar was produced from wheat straw (Triticum aestivum), rice straw (Oryza sativa), and kitchen waste at varying pyrolysis temperatures (300°C-700 °C). The biochars were screened depending on their production and physicochemical properties for the adsorptive removal of arsenic (As). The morphological analysis by Field emission scanning electron microscope revealed a porous biochar surface. Spectroscopic characterization of biochars indicated the co-existence of minerals, carboxyl, carbonyl, amide, and hydroxyl groups, which implies the suitability of biochar to immobilize metal (loid)s from soils. Changes in peaks were observed in Fourier-transform infrared and X-ray diffraction images after As sorption indicating the involvement of chemisorption. The thermogravimetric analysis and a low H/C value derived from the CHNS analyzer confirmed the high stability of biochar. The BET analysis was used to estimate the surface areas of wheat straw (15.8 m2 g-1), rice straw (12.5 m2 g-1), and kitchen waste (2.57 m2 g-1) -derived biochars. Batch sorption studies were performed to optimize experimental parameters for maximum removal of As. Maximum removal of As was observed for wheat straw-derived biochar (pyrolyzed at 500 °C) at 8 mg L-1 initial concentration (IC), 7.5 % dose, 25 °C temperature, and 60 min contact time (83.7 ± 0.06 %); in rice straw-derived biochar (pyrolyzed at 500 °C) at 8 mg L-1 IC, 7.5 % dose, 25 °C temperature, 90 min contact time (83.6 ± 0.37 %); and in kitchen waste-derived biochar (pyrolyzed at 500 °C) at 8 mg L-1 IC, 5 % dose, 25 °C temperature, 60 min contact time (76.7 ± 0.16 %). The sorption model parameters suggested the possibility of chemisorption, physisorption, diffusion, and ion exchange for the removal of As. Therefore, it could be recommended to farmers that instead of disposing or burning straws and waste openly, they could adopt the process of charring to generate livelihood security and mitigation of geogenic contaminants from the soil/water dynamic systems.

Deconjugated butenolide: a versatile building block for asymmetric catalysis.

The wide abundance of γ-lactones in natural products and bioactive targets calls for suitable building blocks for their enantioselective synthesis. ß,γ-Unsaturated γ-butenolides, commonly known as deconjugated butenolides, owing to their easy accessibility and highly reactive nature, have emerged as the synthon of choice during the past decade for the enantioselective synthesis of γ-lactones. Their compatibility under organocatalytic, metal-catalyzed as well as cooperative catalytic conditions has resulted in numerous enantioselective transformations involving deconjugated butenolides. These reactions not only led to enantioenriched γ-lactones, but also various other heterocycles and acyclic compounds through ring-opening and fragmentation of the parent butenolide ring. The purpose of this review is to provide a comprehensive treatise on the catalytic asymmetric reactions of deconjugated butenolides reported so far. This aspect is presented alongside the preparation and reactivity comparison of deconjugated butenolides with other competing synthons of γ-lactones. Limitations of the existing protocols and the possible scope for future development are also discussed.

Hexametaphosphate cross-linked chitosan beads for the eco-efficient removal of organic dyes: Tackling water quality.

There is an increasing trend of developing various low-cost grafted natural amino polysaccharides for the biosorptive removal of noxious dye effluents like Malachite green (MG) and anionic Reactive Red-195 (RR-195) dyes from aqueous solution. Chemically cross-linked chitosan microsphere (CTS-HMP), a promising non-toxic biosorbent possessing high charge density and thermal stability was prepared by using hexametaphosphate as ionic cross-linker. Batch biosorption experiments were carried out under different temperatures (298, 308 and 318 K), pH (2.0-10.0), initial concentrations (25-250 mg L-1), adsorbent dosage (0.01-0.1 g) and contact times (0-180 min) to understand the optimum experimental conditions and simultaneously evaluate the adsorption isotherms and kinetics of CTS-HMP. Biosorption equilibrium was established in 120 and 60 min for MG and RR-195 removal process. The pseudo-equilibrium process was best described by the pseudo-second-order kinetic (R2 ≥ 0.98), Freundlich and Temkin isotherm model (R2 ≥ 0.90). The removal rate of MG and RR-195 gradually increased (69.40 and 148 mg g-1) at 250 mg L-1 of initial concentration till 100 and 50 min of contact period in a single contaminant system, though the removal efficiency of acid dye was ~2 times higher compared to basic dye under optimum conditions (p < 0.05; t-test). Thermodynamic parameters indicated exothermic (MG) and endothermic (RR-195) nature of spontaneous dye removal. The activation energy of sorption (Ea) was <50 kJ mol-1 which highlighted the importance of physical adsorption process. Therefore, the obtained results clearly validate the sustainable utilization of CTS-HMP as a promising functionalized chitosan microparticles/agent for removing dye effluents from the contaminated aqueous phase.

Efficacy of agricultural waste derived biochar for arsenic removal: Tackling water quality in the Indo-Gangetic plain.

Arsenic (As), a geogenic and extremely toxic metalloid can jeopardize terrestrial and aquatic ecosystems through environmental partitioning in natural soil-water compartment, geothermal and marine environments. Although, many researchers have investigated the decontamination potential of different mesoporous engineered bio sorbents for a suite of contaminants, still the removal efficiency of various pyrolyzed agricultural residues needs special attention. In the present study, rice straw derived biochar (RSBC) produced from slow pyrolysis process at 600 °C was used to remove As (V) from aqueous medium. Batch experiments were conducted at room temperature (25 ± 2 °C) under different initial concentrations (10, 30, 50, 100 µg L-1), adsorbent dosages (0.5-5 µg L-1), pH (4.0-10.0) and contact times (0-180 min). The adsorption equilibrium was established in 120 min. Adsorption process mainly followed pseudo-second order kinetics (R2 ≥ 0.96) and Langmuir isotherm models (R2 ≥ 0.99), and the monolayer sorption capacity of 25.6 µg g-1 for As (V) on RSBC was achieved. Among the different adsorbent dosages and initial concentrations used in the present study, 0.2 g L-1 (14.8 µg g-1) and 100 µg L-1 (13.1 µg g-1) were selected as an optimum parameters. A comparative analysis of RSBC with other pyrolyzed waste materials revealed that RSBC had comparable adsorption ability (per unit area). These acidic groups are responsible for the electron exchange (electrostatic attraction, ion-exchange, π-π/n-πinteractions) with the anionic arsenate, which facilitates optimum removal (>60%) at 7 < pH < pHPZC. The future areas of research will focus on decontamination of real wastewater samples containing mixtures of different emerging contaminants and installation of biofilter beds that contains different spent adsorbents/organic substrates (including biochar) for biopurification study in real case scenario.

Catalytic Enantioselective Desymmetrizing Fischer Indolization through Dynamic Kinetic Resolution.

The first catalytic enantioselective Fischer indolization of prochiral diketones containing enantiotopic carbonyl groups is developed and shown to proceed through dynamic kinetic resolution (DKR). Catalyzed by the combination of a spirocyclic chiral phosphoric acid and ZnCl2 (Lewis acid assisted Brønsted acid), this direct approach combines 2,2-disubstituted cyclopentane-1,3-diones with N-protected phenylhydrazines to furnish cyclopenta[b]indole derivatives containing an all-carbon quaternary stereocenter with good to excellent enantioselectivities.

TMDs beyond MoS2 for Electrochemical Energy Storage.

Atomically thin sheets of two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted interest as high capacity electrode materials for electrochemical energy storage devices owing to their unique properties (high surface area, high strength and modulus, faster ion diffusion, and so on), which arise from their layered morphology and diversified chemistry. Nevertheless, low electronic conductivity, poor cycling stability, large structural changes during metal-ion insertion/extraction along with high cost of manufacture are challenges that require further research in order for TMDs to find use in commercial batteries and supercapacitors. Here, a systematic review of cutting-edge research focused on TMD materials beyond the widely studied molybdenum disulfide or MoS2 electrode is reported. Accordingly, a critical overview of the recent progress concerning synthesis methods, physicochemical and electrochemical properties is given. Trends and opportunities that may contribute to state-of-the-art research are also discussed.

Biomedical application, drug delivery and metabolic pathway of antiviral nanotherapeutics for combating viral pandemic: A review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a neoteric virus belonging to the beta coronavirus class has created a global health concern, responsible for an outbreak of severe acute respiratory illness, the COVID-19 pandemic. Infected hosts exhibit diverse clinical features, ranging from asymptomatic to severe symptoms in their genital organs, respiratory, digestive, and circulatory systems. Considering the high transmissibility (R0: ≤6.0) compared to Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, the quest for the clinical development of suitable antiviral nanotherapeutics (NTPs) is incessant. We are presenting a systematic review of the literature published between 2003 and 2020 to validate the hypothesis that the pharmacokinetics, collateral acute/chronic side effects of nano drugs and spike proteins arrangement of coronaviruses can revolutionize the therapeutic approach to cure COVID-19. Our aim is also to critically assess the slow release kinetics and specific target site chemical synthesis influenced competence of NTPs and nanotoxicity based antiviral actions, which are commonly exploited in the synthesis of modulated nanomedicines. The pathogenesis of novel virulent pathogens at the cellular and molecular levels are also considered, which is of utmost importance to characterize the emerging nano-drug agents as diagnostics or therapeutics or viral entry inhibitors. Such types of approaches trigger the scientists and policymakers in the development of a conceptual framework of nano-biotechnology by linking nanoscience and virology to present a smart molecular diagnosis/treatment for pandemic viral infections.

TRIM5α SPRY/coiled-coil interactions optimize avid retroviral capsid recognition.

Restriction factors are important components of intrinsic cellular defense mechanisms against viral pathogens. TRIM5α is a restriction factor that intercepts the incoming capsid cores of retroviruses such as HIV and provides an effective species-specific barrier to retroviral infection. The TRIM5α SPRY domain directly binds the capsid with only very weak, millimolar-level affinity, and productive capsid recognition therefore requires both TRIM5α dimerization and assembly of the dimers into a multivalent hexagonal lattice to promote avid binding. Here, we explore the important unresolved question of whether the SPRY domains are flexibly linked to the TRIM lattice or more precisely positioned to maximize avidity. Biochemical and biophysical experiments indicate that the linker segment connecting the SPRY domain to the coiled-coil domain adopts an α-helical fold, and that this helical portion mediates interactions between the two domains. Targeted mutations were generated to disrupt the putative packing interface without affecting dimerization or higher-order assembly, and we identified mutant proteins that were nevertheless deficient in capsid binding in vitro and restriction activity in cells. Our studies therefore support a model wherein substantial avidity gains during assembly-mediated capsid recognition by TRIM5α come in part from tailored spacing of tethered recognition domains.

Sustainable removal of pernicious arsenic and cadmium by a novel composite of MnO2 impregnated alginate beads: A cost-effective approach for wastewater treatment.

There is a dire necessity of developing low cost waste water treatment systems, for the efficient removal of noxious heavy metals (and metalloids) such as Arsenic (As) and Cadmium (Cd). Magnetic biopolymer (CABs-MO) was synthesized by the entrapment of nanocrystalline MnO2 in the polymeric microcapsules of calcium alginate (CABs). Batch experiments were conducted under constant pH (6.5), temperature (25OC), different initial concentrations (30-300 mg L-1) and contact times (0-48 h) to study the adsorption isotherms and removal kinetics of pristine (CABs) and hybrid biopolymer (CABs-MO) for the removal of As and Cd. The pseudo-equilibrium process was mathematically well explained by the pseudo-second-order kinetic (R2 ≥ 0.99) and Langmuir isotherm model (R2 ≥ 0.99) with the highest monolayer sorption capacity of 63.6 mg g-1 for Cd on CABs-MO. The As removal rate was maximum up to 6.5 mg g-1 after 12 h of contact period in a single contaminant system than in the mixed contaminant (As + Cd) system (0.8 mg g-1), though the effect was non-significant for Cd (p < 0.05; t-test). The performance of the 10 mM HCl as a regenerating agent was superior (for As in comparison to Cd, p < 0.05; t-test) compared to distilled water (DW) through three to five regeneration cycles. Therefore, the obtained results clearly validate the feasibility of CABs-MO as a potential promising adsorbent for removing metal contaminants from the wastewater. Further research is required to study the decontamination of emerging contaminants with such novel composite beads characterized by varied physico-chemical properties.

Direct Catalytic Enantioselective Vinylogous Aldol Reaction of Allyl Ketones to Pyrazole-4,5-diones.

The first catalytic enantioselective vinylogous nucleophilic addition to pyrazole-4,5-diones is reported. Using quinine-derived bifunctional tertiary amino-amide as the catalyst, this direct aldol reaction of allyl ketones is shown to proceed exclusively in γ- and E-selective manner to generate pyrazolone derivatives, bearing an oxygen-containing quaternary stereogenic center, in good yields with moderate to high enantioselectivities (up to 97:3 er).

Catalytic Enantioselective C-C Bond-Forming Reactions of Deconjugated Butyrolactams: Michael Addition to α,ß-Unsaturated Aldehydes and Ketones.

Nucleophilic reactivity of deconjugated butyrolactams has been demonstrated for enantioselective Michael additions to α,ß-unsaturated aldehydes and ketones. These reactions are catalyzed by diphenylprolinol silyl ether and trans-1,2-diaminocyclohexane-derived bifunctional primary aminothiourea, respectively, producing the Michael adducts with moderate diastereoselectivities and good to excellent enantioselectivities (up to 99:1 er). Unlike in the case of structurally related deconjugated butenolides where vinylogous addition is prevalent, an exclusive α-addition is observed for deconjugated butyrolactams.

Catalytic Enantioselective Synthesis of 3,4-Unsubstituted Thiochromenes through Sulfa-Michael/Julia-Kocienski Olefination Cascade Reaction.

A highly enantioselective cascade sulfa-Michael/Julia-Kocienski olefination reaction between 2-mercaptobenzaldehydes and ß-substituted vinyl PT-sulfones has been realized for the synthesis of 3,4-unsubstituted 2H-thiochromenes. This reaction, catalyzed by diphenylprolinol TMS ether, proceeds through an aromatic iminium intermediate and furnishes a wide range of 2-substiuted 2H-thiochromenes with excellent enantioselectivities (up to 99:1 er).