Acid Residues Research Articles

Deciphering the Binding Interactions between Acinetobacter baumannii ACP and β-ketoacyl ACP Synthase III to Improve Antibiotic Targeting Using NMR Spectroscopy.

Fatty acid synthesis is essential for bacterial viability. Thus, fatty acid synthases (FASs) represent effective targets for antibiotics. Nevertheless, multidrug-resistant bacteria, including the human opportunistic bacteria, Acinetobacter baumannii, are emerging threats. Meanwhile, the FAS pathway of A. baumannii is relatively unexplored. Considering that acyl carrier protein (ACP) has an important role in the delivery of fatty acyl intermediates to other FAS enzymes, we elucidated the solution structure of A. baumannii ACP (AbACP) and, using NMR spectroscopy, investigated its interactions with β-ketoacyl ACP synthase III (AbKAS III), which initiates fatty acid elongation. The results show that AbACP comprises four helices, while Ca2+ reduces the electrostatic repulsion between acid residues, and the unconserved F47 plays a key role in thermal stability. Moreover, AbACP exhibits flexibility near the hydrophobic cavity entrance from D59 to T65, as well as in the α1α2 loop region. Further, F29 and A69 participate in slow exchanges, which may be related to shuttling of the growing acyl chain. Additionally, electrostatic interactions occur between the α2 and α3-helix of ACP and AbKAS III, while the hydrophobic interactions through the ACP α2-helix are seemingly important. Our study provides insights for development of potent antibiotics capable of inhibiting A. baumannii FAS protein–protein interactions.

Re-expression of glucuronyl C5-epimerase in the mutant MEF cells increases heparan sulfate epimerization but has no influence on the Golgi localization and enzymatic activity of 2-O-sulfotransferase.

Heparan sulfate (HS) is a linear and complex polysaccharide that modulates the biological activities through protein recognition and interaction. Evidence indicates that protein-binding properties of HS are largely dependent on distinctive sulfation and epimerization patterns that are modified by a series of Golgi-localized enzymes. In particular, the glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) residues to L-iduronic acid (IdoA) and 2-O-sulfotransferase (2OST) catalyzes sulfation at C2 position of IdoA and rarely GlcA residues. Mice lacking both Hsepi and 2OST display multiple development defects, indicating the importance of IdoA in HS. Here, to gain greater insights of HS structure-function relationships, as well as a better understanding of the regulatory mechanisms of Hsepi and 2OST, the fine structure and cellular signaling functions of HS were investigated after restoration of Hsepi in the mutant mouse embryonic fibroblast (MEF) cells. Introduction of Hsepi into the Hsepi mutant MEF cells led to robustly increased proportion of IdoA residues, which rescued the cell signaling in response to fibroblast growth factor 2. However, we found that Hsepi knockout had no influence on either cellular transport or enzymatic activity of 2OST in the MEF cells, which is not in accord with the findings suggesting that the enzymatic activity and cellular transport of 2OST and Hsepi might be differently regulated.

Rhodamines with a Chloronicotinic Acid Fragment for Live Cell Superresolution STED Microscopy*.

Formylation of 2,6‐dichloro‐5‐R‐nicotinic acids at C‐4 followed by condensation with 3‐hydroxy‐N,N‐dimethylaniline gave analogs of the popular TAMRA fluorescent dye with a 2,6‐dichloro‐5‐R‐nicotinic acid residues (R=H, F). The following reaction with thioglycolic acid is selective, involves only one chlorine atom at the carbon between pyridine nitrogen and the carboxylic acid group and affords new rhodamine dyes absorbing at 564/ 573 nm and emitting at 584/ 597 nm (R=H/ F, in aq. PBS). Conjugates of the dyes with “small molecules” provided specific labeling (covalent and non‐covalent) of organelles as well as of components of the cytoskeleton in living cells and were combined with fluorescent probes prepared from 610CP and SiR dyes and applied in two‐color STED microscopy with a 775 nm STED laser.

Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids.

The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)n-O2Oc-NH2, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]8-O2Oc-NH2 and typical for large proteins.

Pb Recycling Through Leaching, Precipitation, and Cementation from Zinc Plant Residue

This paper presents the hydrometallurgical methods used for the recovery of concentrate and metallic lead from zinc plant residue (ZPR). The ZPR mainly consisting of 9.5% Pb and 7.5% Zn was initially leached by sulfuric acid under the following conditions: leaching temperature 90 °C, leaching time 90 min., sulfuric acid concentration 200 g/l, and solid/liquid ratio 1/5. The zinc recovery obtained was 92.8%, which was finally directed to solvent extraction circuit to produce zinc cathode. Then acidic residue was subjected to alkaline leaching, using sodium hydroxide (NaOH). The lead recovery obtained was 92.58%. For precipitation method by using NaClO, the effects of three important factors including (NaClO/solution) ratio, temperature, and precipitation time were studied and reported. As a result, lead was precipitated in the form of PbO2 with concentrated grade of 72.03% and recovery of 92.31%. Furthermore, aluminum was used for cementation process to produce metallic Pb with grade of 96.11% and total recovery of 87.17%.

Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1

Acid-sensing ion channels (ASICs) are proton-gated cation channels critical for neuronal functions. Studies of ASIC1, a major ASIC isoform and proton sensor, have identified acidic pocket, an extracellular region enriched in acidic residues, as a key participant in channel gating. While binding to this region by the venom peptide psalmotoxin modulates channel gating, molecular and structural mechanisms of ASIC gating modulation by small molecules are poorly understood. Here, combining functional, crystallographic, computational and mutational approaches, we show that two structurally distinct small molecules potently and allosterically inhibit channel activation and desensitization by binding at the acidic pocket and stabilizing the closed state of rat/chicken ASIC1. Our work identifies a previously unidentified binding site, elucidates a molecular mechanism of small molecule modulation of ASIC gating, and demonstrates directly the structural basis of such modulation, providing mechanistic and structural insight into ASIC gating, modulation and therapeutic targeting.

Structural characterization of fondaparinux interaction with per-6-amino-beta-cyclodextrin: An NMR and MS study

The highly anionic synthetic pentasaccharide fondaparinux (FDPX) – representing the antithrombin binding sequence of heparin – is in clinical use as a potent anticoagulant. Contrary to the unfractionated heparin, FDPX lacks potent antidote completely reversing its anticoagulant activity, therefore it is of great importance to identify new structures exhibiting strong intermolecular interactions towards FDPX. The polycationic heptakis(6-amino-6-deoxy)-beta-cyclodextrin (NH2-β-CD) can serve as an excellent model compound to mimic these interactions between the oppositely charged oligosaccharides. Herein, extensive NMR spectroscopic and nano-electrospray ionization mass spectrometric (nESI-MS) studies were conducted to understand the molecular-level interactions in the FDPX - NH2-β-CD systems. NMR experiments were performed at pD 7.4 and 2.0. Job’s method of continuous variation and 1H NMR titration experiments suggested the formation of FDPX∙NH2-β-CD complex at pD 7.4, while the presence of multiple complexes was assumed at pD 2.0. Stability constants were determined by separate 1H NMR titrations, yielding log β11=3.65 ± 0.02 at pD 7.4, while log β11 ≥ 4.9 value suggested a high-affinity system at pD 2.0. 2D NOESY NMR studies indicated spatial proximities between the anomeric resonance α-l-iduronic acid residue and the cyclodextrin’s methylene unit in the proximity of the cationic amino function. Acidic degradation of FDPX was investigated by NMR and MS for the first time in detail confirming that desulfation occurs involving one to two sulfate moieties. The desulfation of FDPX was inhibited by the cationic cyclodextrin in the case of equimolar ratio at pD 2.0. This is the first report on the stabilizing effect of cyclodextrin complexation on heparin degradation.

ID-TIMS zircon U–Pb geochronology of the Camel Donga eucrite

Eucrite meteorites are considered to originate from the upper crust of asteroid 4-Vesta. These differentiated basaltic meteorites commonly contain accessory zircons with grain sizes smaller than 20–30 μm in diameter. U–Pb zircon dating using secondary ion mass spectrometry (SIMS) revealed that initial magmatism and global thermal metamorphism occurred in the Vestan crust ~4550–4555 million year ago (Ma). To improve the temporal resolution in order to distinguish zircons grown during different thermal events in the early stage of crustal evolution of Vesta, we have applied a chemical abrasion-based method for extracting small zircon crystals from bulk meteorite samples and obtained high-precision isotope dilution-thermal ionization mass spectrometry (ID-TIMS) U–Pb dates for zircons from the Camel Donga eucrite. Some of the Camel Donga zircons occur in contact with ilmenite, implying that they have formed by exsolution of ilmenite followed by reaction with silica during high temperature metamorphism. Raman measurements indicate that the zircons are moderately radiation damaged and that high temperature annealing (900 °C for 48 h) is likely to improve their crystallinities. Zircons separated from acid residues after dissolving other minerals in a mixture of hydrofluoric and nitric acid experienced U–Pb and Pb isotope fractionation during the acid treatment. High temperature annealing prior to acid extraction efficiently suppresses Pb isotope fractionation resulting in accurate and precise 207Pb–206Pb dates. The weighted mean 207Pb–206Pb date of the annealed zircons is 4552.56 ± 0.69 Ma (2σ), which is significantly older than that of Camel Donga zircons previously obtained by SIMS (4531 ± 10 Ma) but is consistent with 207Pb–206Pb dates of zircons in the other eucrites. Thus, the Camel Donga eucrite zircons formed during initial magmatism or global thermal metamorphism in the early stage of Vestan crustal formation.

Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A

Amyloid A (AA) amyloidosis is a condition in which amyloid fibrils characterized by a linear morphology and a cross-β structure accumulate and are deposited extracellularly in organs, resulting in chronic inflammatory diseases and infections. The incidence of AA amyloidosis is high in humans and several animal species. Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. Amyloid enhancing factor (AEF) serves as a seed for fibril formation and shortens the onset of AA amyloidosis sharply. In this study, we examined whether AEFs extracted and purified from five animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA (mSAA) protein aggregation in vitro using quantum-dot (QD) nanoprobes to visualize the aggregation. The results showed that AEFs shortened and promoted mSAA aggregation. In addition, mouse and cat AEFs showed higher mSAA aggregation-promoting activity than the camel, cattle, and goat AEFs. Interestingly, homology analysis of SAA in these five animal species revealed a more similar amino acid sequence homology between mouse and cat than between other animal species. Furthermore, a detailed comparison of amino acid sequences suggested that it was important to mSAA aggregation-promoting activity that the 48th amino acid was a basic residue (Lys) and the 125th amino acid was an acidic residue (Asp or Glu). These data imply that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, and may provide a new understanding of the pathogenesis of amyloidosis.

Structural Characterization of the Interaction between the αMI-Domain of the Integrin Mac-1 (αMβ2) and the Cytokine Pleiotrophin.

Integrin Mac-1 (αMβ2) is an adhesion receptor vital to many functions of myeloid leukocytes. It is also the most promiscuous member of the integrin family capable of recognizing a broad range of ligands. In particular, its ligand-binding αMI-domain is known to bind cationic proteins/peptides depleted in acidic residues. This contradicts the canonical ligand-binding mechanism of αI-domains, which requires an acidic amino acid in the ligand to coordinate the divalent cation within the metal ion-dependent adhesion site (MIDAS) of αI-domains. The lack of acidic amino acids in the αMI-domain-binding sequences suggests the existence of an as-yet uncharacterized interaction mechanism. In the present study, we analyzed interactions of the αMI-domain with a representative Mac-1 ligand, the cationic cytokine pleiotrophin (PTN). Through NMR chemical shift perturbation analysis, cross saturation, NOESY, and mutagenesis studies, we found the interaction between the αMI-domain and PTN is divalent cation-independent and mediated mostly by hydrophobic contacts between the N-terminal domain of PTN and residues in the α5-β5 loop of αMI-domain. The observation that increased ionic strength weakens the interaction between the proteins indicates electrostatic forces may also play a significant role in the binding. On the basis of the results from these experiments, we formulated a model of the interaction between the αMI-domain and PTN.

Mechanism of hERG inhibition by gating-modifier toxin, APETx1, deduced by functional characterization

BackgroundHuman ether-à-go-go-related gene potassium channel 1 (hERG) is a voltage-gated potassium channel, the voltage-sensing domain (VSD) of which is targeted by a gating-modifier toxin, APETx1. APETx1 is a 42-residue peptide toxin of sea anemone Anthopleura elegantissima and inhibits hERG by stabilizing the resting state. A previous study that conducted cysteine-scanning analysis of hERG identified two residues in the S3-S4 region of the VSD that play important roles in hERG inhibition by APETx1. However, mutational analysis of APETx1 could not be conducted as only natural resources have been available until now. Therefore, it remains unclear where and how APETx1 interacts with the VSD in the resting state.ResultsWe established a method for preparing recombinant APETx1 and determined the NMR structure of the recombinant APETx1, which is structurally equivalent to the natural product. Electrophysiological analyses using wild type and mutants of APETx1 and hERG revealed that their hydrophobic residues, F15, Y32, F33, and L34, in APETx1, and F508 and I521 in hERG, in addition to a previously reported acidic hERG residue, E518, play key roles in the inhibition of hERG by APETx1. Our hypothetical docking models of the APETx1-VSD complex satisfied the results of mutational analysis.ConclusionsThe present study identified the key residues of APETx1 and hERG that are involved in hERG inhibition by APETx1. These results would help advance understanding of the inhibitory mechanism of APETx1, which could provide a structural basis for designing novel ligands targeting the VSDs of KV channels.

Variability in linear polypeptide stabilizes proteoglycan than zinc finger protein in vascular smooth muscle cells: An In Silico approach

Background: Structural and physicochemical topologies of proteins play a considerable role in differentiating the functional properties of the biological system. We aimed to study the physicochemical similarities, structural and functional differences of versican (VCAN) and early growth response (Egr) proteins involved in vascular injuries. Methods: For the primary structure prediction, the proteomic tools Expasy's Protparam is used, likewise, for secondary structure and content prediction SOPM and SOPMA tool is used. The transmembrane regions in VCAN and EGR proteins are predicted through SOSUI (Classification and Secondary Structure Prediction of Membrane Proteins) server. The CYSREC tool is used to identify the presence of disulphide bonds in all the VCAN and EGR proteins, additionally through homology modelling the disulphide bonds are visualized and structure of the modelled proteins are validated through Rampage (Ramachandran plot), ProQ (Protein Quality Server) and ProSA (Protein Structure Analysis) server. Results: VCAN and Egr proteins resemble hydrophilic in nature, similarly negative score of the grand average of hydropathicity index confirms hydrophilic nature. The maximum molecular weight for VCAN is observed as 39265 and 61623 Dalton for EGR protein. VCAN proteins showed a higher level of basic residues except Q86W61, while all the Egr proteins were acidic residues. The extinction coefficient (EC) has unique absorbance at 280 nm wavelength. Based on the aliphatic index (AI ≥ 45) and instability index (II ≥ 40) most of the VCAN and Egr proteins were unstable. The Classification and Secondary Structure Prediction of Membrane Proteins server classifies all Egr and few VCAN and proteins are soluble nature. Secondary structure content prediction and SOPM server show most of the VCAN proteins are beta sheets and many Egr proteins are alpha-helical, while few with mixed structures. Besides these differences, the VCAN protein stability was identified by most probable disulfide (SS) bridges using CYS_REC tool and confirmed by homology modeling in tertiary structure. Whereas the probable disulfide bonds in Egr proteins were not identified. Conclusion: The findings with these functional and structural properties will add an extra room in understanding their dual role.

Conformational switching, refolding and membrane insertion of the diphtheria toxin translocation domain.

Diphtheria toxin is among many bacterial toxins that utilize the endosomal pathway of cellular entry, which is ensured by the bridging of the endosomal membrane by the toxin's translocation (T) domain. Endosomal acidification triggers a series of conformational changes of the T-domain, that take place first in aqueous and subsequently in membranous milieu. These rearrangements ultimately result in establishing membrane-inserted conformation(s) and translocation of the catalytic moiety of the toxin into the cytoplasm. We discuss here the strategy for combining site-selective labeling with various spectroscopic methods to characterize structural and thermodynamic aspects of protonation-dependent conformational switching and membrane insertion of the diphtheria toxin T-domain. Among the discussed methods are FRET, FCS and depth-dependent fluorescence quenching with lipid-attached bromine atoms and spin probes. The membrane-insertion pathway of the T-domain contains multiple intermediates and is governed by staggered pH-dependent transitions involving protonation of histidines and acidic residues. Presented data demonstrate that the lipid bilayer plays an active part in T-domain functioning and that the so-called Open-Channel State does not constitute the translocation pathway, but is likely to be a byproduct of the translocation. The spectroscopic approaches presented here are broadly applicable to many other systems of physiological and biomedical interest for which conformational changes can lead to membrane insertion (e.g., other bacterial toxins, host defense peptides, tumor-targeting pHLIP peptides and members of Bcl-2 family of apoptotic regulators).

A quick and inexpensive method to determine 2,4-dichlorophenoxyacetic acid residues in water samples by HPLC

A quick and inexpensive method to determine 2,4-dichlorophenoxyacetic acid residues in water samples by HPLC

Молочна продуктивність кіз зааненської породи за згодовування органічної кормової добавки гумінової природи

The results of the study of Saanen goats milk productivity while feeding humic origin organic feed supplement of «VitaHum» are presented in the paper. Studying milk productivity of different goat breeds, as well as using balanced rations of biologically active feed supplements for therapeutic and prophylactic properties and improving metabolic processes and body functions, are important issues for animal breeding industry, since goat husbandry in Ukraine is in a state of formation. «VitaHum» is completely different from existing biologically active peat supplements on the market because it is received not as a result of peat hydrolysis by alkalis or acids, but by a natural way of chelation. It does not contain humic acids sodium salts with alkali residues with which no reaction had taken place, but residues of amino acids, peptides, carboxylic acids and other useful substances in pure «natural» organic form. This feed supplement meets European standards of organic products. It was found that with the industrial technology of the animal management and feeding with mixed diets when using humic origin feed supplement «VitaHum» during the entire lactation period, milk yield was increased by 15.9% or 137.3 kg, milk protein content by 0.11 abs. percent. However, the goats from the control group had the advantage in milk fat content by 0.09 abs. percent (P > 0.999). The maximum average daily milk yield of 3.55 kg was observed in the second experimental group of goats, which received feed supplements «VitaHum» in addition to the main diet. However, as a result of a significant advantage in milk yield from goats of the experimental group, a noticeably higher amount of both milk protein and milk fat mass fraction was obtained by 5.94 kg and 4.63 kg, respectively. Analysis of the qualitative milk composition of the experimental goats showed that the percentage of milk solids non-fat (MSNF) was in the range of 8.45–8.58%, and the content of somatic cells in the milk of control group animals was higher by 7.05%. The qualitative milk composition was quite satisfactory for this breed of goats, as the milk fat mass fraction was 3.94–4.03% and protein one 3.52–3.63%. The ratio of fat and protein at the level of 1.15–1.09 units indicated a good physiological state of the digestive system of the Saanen breed goats.

Fuzzy Association of an Intrinsically Disordered Protein with Acidic Membranes.

Many physiological and pathophysiological processes, including Mycobacterium tuberculosis (Mtb) cell division, may involve fuzzy membrane association by proteins via intrinsically disordered regions. The fuzziness is extreme when the conformation and pose of the bound protein and the composition of the proximal lipids are all highly dynamic. Here, we tackled the challenge in characterizing the extreme fuzzy membrane association of the disordered, cytoplasmic N-terminal region (NT) of ChiZ, an Mtb divisome protein, by combining solution and solid-state NMR spectroscopy and molecular dynamics simulations. While membrane-associated NT does not gain any secondary structure, its interactions with lipids are not random, but formed largely by Arg residues predominantly in the second, conserved half of the NT sequence. As NT frolics on the membrane, lipids quickly redistribute, with acidic lipids, relative to zwitterionic lipids, preferentially taking up Arg-proximal positions. The asymmetric engagement of NT arises partly from competition between acidic lipids and acidic residues, all in the first half of NT, for Arg interactions. This asymmetry is accentuated by membrane insertion of the downstream transmembrane helix. This type of semispecific molecular recognition may be a general mechanism by which disordered proteins target membranes.

Pyridine Derivatives of Acridine and Quinoline

A convenient one-pot approach was proposed for the synthesis of new derivatives of 8,9,10,12tetrahydrobenzo[a]acridin-11(7H)-one and 10,12-dihydrobenzo[f]pyrimido[4,5-b]quinoline-9,11(7H,8H)-dione containing residues of nicotinic and isonicotinic acids covalently attached via ester groups in different positions of the aromatic core. Quaternary ammonium salts of the synthesized acridine derivatives as well as a metal complex with palladium PdLCl2 were obtained. These compounds contain a number of pharmacophore groups so going to be promising potential drugs with antimicrobial, antiviral, and antitumor activity.

Structural analysis of the core oligosaccharides from Fusobacterium nucleatum lipopolysaccharides

Fusobacterium nucleatum is a gram-negative bacterium, part of the normal human microflora. It is associated with various health complications, including periodontitis and colorectal cancer. Its surface is covered with lipopolysaccharide, which interacts with the immune system and can be involved in various processes in health and disease conditions. Here we present the results of structural analysis of core oligosaccharides from the lipopolysaccharides of several strains of F. nucleatum. Pure compounds were isolated using mild acid hydrolysis or alkaline deacylation of the lipopolysaccharides and analyzed by NMR spectroscopy, mass-spectrometry and chemical methods. All cores analyzed had a common octasaccharide region, including five heptose residues and a non-phosphorylated 3-deoxy-d-manno-oct-2-ulosonic acid residue. The common region is substituted with different additional components specific for each strain. By structure type the F. nucleatum core is similar to that produced by Aeromonas.

Complicating Infections Associated with Common Endemic Human Respiratory Coronaviruses.

Coronaviruses OC43, 229E, NL63, and HKU1 are endemic human respiratory coronaviruses that typically cause mild to moderate upper respiratory infections, similar to the common cold. They also may cause simple and complicated lower respiratory infections, otitis media, asthma exacerbations, gastroenteritis, and a few systemic complications. These viruses are usually seasonal (with winter dominance) and affect nearly all age groups. The seasonal and annual variation in virus prevalence has implications for understanding the concept of acquired immunity and its persistence or diminution. Coronaviruses generally have outbreak potential in susceptible populations of any age, particularly in patients with comorbidities, who tend to have increased clinical disease. These 4 coronaviruses are often found in the context of what appears to be coinfection with other pathogens, but especially other viruses. If coronaviruses are not specifically tested for, the sole detection of a viral copathogen would suggest the pathogen is the causative agent, when a coronavirus may be culpable, or both. The detection of these viruses in circumstances where respiratory viruses are generally sought in clinical samples is, therefore, justified. These pathogens can be chronically shed from the respiratory tract, which is more likely to occur among immunocompromised and complicated patients. These viruses share the potential for genetic drift. The genome is among the largest of RNA viruses, and the capability of these viruses to further change is likely underestimated. Given the potential disease among humans, it is justified to search for effective antiviral chemotherapy for these viruses and to consider uses in niche situations should effective therapy be defined. Whereas SARS-CoV-2 may follow the epidemiological pattern of SARS-CoV and extinguish slowly over time, there is yet concern that SARS-CoV-2 may establish itself as an endemic human respiratory coronavirus similar to OC43, 2299E, NL63, and HKU1. Until sufficient data are acquired to better understand the potential of SARS-CoV-2, continued work on antiviral therapy and vaccination is imperative.

Heterocyclization of amino alcohols into saturated cyclic quaternary ammonium salts

Cyclodehydration of available N-alkylethanolamines with aldehydes and simultaneous or subsequent quaternization afford functionalized quaternary ammonium salts of N-nitroimidazolidine, oxazolidine and annulated bismorpholine type. Further replacement of their anions with residues of explosive acids provides a series of energyintensive quaternary salts with a rich hydrogen content possessing satisfactory energy characteristics and sufficiently high thermal stability.