SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a candidate vaccine antigen that binds angiotensin-converting enzyme 2 (ACE2), leading to virus entry. Here, it is shown that rapid conversion of recombinant RBD into particulate form via admixing with liposomes containing cobalt-porphyrin-phospholipid (CoPoP) potently enhances the functional antibody response. Antigen binding via His-tag insertion into the CoPoP bilayer results in a serum-stable and conformationally intact display of the RBD on the liposome surface. Compared to other vaccine formulations, immunization using CoPoP liposomes admixed with recombinant RBD induces multiple orders of magnitude higher levels of antibody titers in mice that neutralize pseudovirus cell entry, block RBD interaction with ACE2, and inhibit live virus replication. Enhanced immunogenicity can be accounted for by greater RBD uptake into antigen-presenting cells in particulate form and improved immune cell infiltration in draining lymph nodes. QS-21 inclusion in the liposomes results in an enhanced antigen-specific polyfunctional T cell response. In mice, high dose immunization results in minimal local reactogenicity, is well-tolerated, and does not elevate serum cobalt levels. Taken together, these results confirm that particulate presentation strategies for the RBD immunogen should be considered for inducing strongly neutralizing antibody responses against SARS-CoV-2.     

Nanoparticle approaches against SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the worst pandemic disease of the current millennium. To address this crisis, therapeutic nanoparticles, including inorganic nanoparticles, lipid nanoparticles, polymeric nanoparticles, virus-like nanoparticles, and cell membrane-coated nanoparticles, have all offered compelling antiviral strategies. This article reviews these strategies in three categories: (1) nanoparticle-enabled detection of SARS-CoV-2, (2) nanoparticle-based treatment for COVID-19, and (3) nanoparticle vaccines against SARS-CoV-2. We discuss how nanoparticles are tailor-made to biointerface with the host and the virus in each category. For each nanoparticle design, we highlight its structure–function relationship that enables effective antiviral activity. Overall, nanoparticles bring numerous new opportunities to improve our response to the current COVID-19 pandemic and enhance our preparedness for future viral outbreaks.     

Efficient Targeted Delivery of Bifunctional Circular Aptamer-ASO Chimera to Suppress the SARS-CoV-2 Proliferation and Inflammation

Inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and excessive inflammation is the current task in the prevention and treatment of corona vireus disease 2019 (COVID-19). Here, a dual-function circular aptamer-ASO chimera (circSApt-NASO) is designed to suppress SARS-CoV-2 replication and inflammation. The chemically unmodified circSApt-NASO exhibits high serum stability by artificial cyclization. It is also demonstrated that the SApt binding to spike protein enables the chimera to be efficiently delivered into the host cells expressing ACE2 along with the infection of SARS-CoV-2. Among them, the SApt potently inhibits spike-induced inflammation. The NASO targeting to silence N genes not only display robust anti-N-induced inflammatory activity, but also achieve efficient inhibition of SARS-CoV-2 replication. Overall, benefiting from the high stability of the cyclization, antispike aptamer-dependent, and viral infection-mediate targeted delivery, the circSApt-NASO displays robust potential against authentic SARS-CoV-2 and Omicron, providing a promising specific anti-inflammatory and antiproliferative reagent for therapeutic COVID-19.     

Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants

As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C₆₀ fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit infection of SARS-CoV-2 variants in vitro. Effective inhibitory concentrations in the millimolar range highlight the significance of bare fullerene's hydrophobic moiety and electrostatic interactions of polysulfates with surface proteins of SARS-CoV-2. Furthermore, microscale thermophoresis measurements support that fullerene linear polyglycerol sulfates interact with the SARS-CoV-2 virus via its spike protein, and highlight importance of electrostatic interactions within it. All-atom molecular dynamics simulations reveal that the fullerene binding site is situated close to the receptor binding domain, within 4 nm of polyglycerol sulfate binding sites, feasibly allowing both portions of the material to interact simultaneously.     

MXene-Based Aptameric Fluorosensor for Sensitive and Rapid Detection of COVID-19 (Small 23/2023)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused COVID-19 pandemic has rapidly escalated into the largest global health emergency, which pushes to develop detection kits for the detection of COVID-19 with high sensitivity, specificity, and fast analysis. Here, aptamer-functionalized MXene nanosheet is demonstrated as a novel bionanosensor that detects COVID-19. Upon binding to the spike receptor binding domain of SARS-CoV-2, the aptamer probe is released from MXene surface restoring the quenched fluorescence. The performances of the fluorosensor are evaluated using antigen protein, cultured virus, and swab specimens from COVID-19 patients. It is evidenced that this sensor can detect SARS-CoV-2 spike protein at final concentration of 38.9 fg mL⁻¹ and SARS-CoV-2 pseudovirus (limit of detection: 7.2 copies) within 30 min. Its application for clinical samples analysis is also demonstrated successfully. This work offers an effective sensing platform for sensitive and rapid detection of COVID-19 with high specificity.     

Analyte templating: enhancing the enantioselectivity of chiral selectors upon incorporation into organic polymer environments

A simple strategy for preserving and enhancing the chiral recognition capacity of polymer-embedded chiral selectors is proposed, capitalizing on a temporary blockage of the receptor binding site with tightly binding analytes during the polymerization process. We demonstrate that the copolymerization of a quinine tert-butylcarbamate selector monomer with chiral (and achiral) 3,5-dichlorobenzoyl amino acids allows one to control to a certain extent the binding characteristics of the resultant polymeric chiral stationary phases. The structural and stereochemical requirements of the templating analytes for maximizing the chiral recognition capacity of the polymer-embedded selectors are probed. The chromatographic chiral recognition characteristics of the analyte-templated polymeric chiral stationary phases are analyzed with respect to binding capacities and affinities and compared to those obtained with a conventional silica-based surface-grafted reference material. Changes in substrate-specific enantioselectivity originating from analyte templating are also addressed.     

Potential Inhibitory Effect of Vitamins Against COVID-19

Coronavirus disease 2019 (COVID-19) is a current pandemic that has affected more than 195 countries worldwide. In this severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, when treatment strategies are not yet clear and vaccines are not available, vitamins are an excellent choice to protect against this viral infection. The rationale behind this study was to examine the inhibitory effect of vitamins B, C, and D against the main protease of SARSCoV-2 and angiotensin-converting enzyme 2 (ACE2), which have critical rolesin the immune system. Molecular docking, performed by using MOE-Dock of the Chemical Computing Group, was used to understand the mechanism. The vitamins all docked within the active sites of the M^pro (PDB ID:6LU7) and ACE2 receptor proteins (PDB ID:6VW1). Vitamins B and C delivered maximum energy scores against both targets, while vitamin D displayed a binding energy score of −7.9532 kcal/mol for M^pro and −7.9297 for ACE2. The efficiency of all three vitamins is higher than the binding energy score of chloroquine (−6.889 kcal/mol), which is now under clinical trials. The use of vitamins is beneficial, being immune system restorative, and they also act as anti-COVID agents. Although the potential beneficial effects of vitamin B and C are revealed through docking studies, further clinical trials are required for the validation of these results.     

阳离子有机高分子絮凝剂的研究进展

絮凝沉淀法是广泛使用的水处理技术之一,而絮凝剂是絮凝法水处理的核心技术.与无机絮凝剂相比,有机高分子絮凝剂具有用量少、成本低、毒性小等优点,因此它的开发应用越来越受关注.而阳离子有机高分子絮凝剂由于带有可离解的阳离子更适合于水处理应用.本文介绍了阳离子聚丙烯酰胺类、天然高分子改性类、烷基烯丙基卤化铵类和环氧氯丙烷与胺反...     

用于新型冠状病毒检测的纳米材料及生物传感技术

新型冠状病毒肺炎(Corona Virus Disease 2019, COVID-19)疫情大流行引起全球对此重大突发公共卫生事件的高度关注。新型冠状病毒(SARS-CoV-2)经过多次突变,出现传染速度加快、免疫逃逸、隐匿性传播等特性,令防控形势至今仍异常严峻。对患者的早发现、早隔离仍然是目前最有效的防控措施。因此,迫切需要快速、高灵敏的检测手段来甄别此病毒,以便及早识别感染者。本文简要介绍了SARS-CoV-2的一般特征,并针对核酸、抗体、抗原及病原体作为检测靶标的不同检测手段及最新进展进行分类概述;对一些光学、电学、磁学以及可视化的新型纳米传感器在SARS-CoV-2检测技术上的应用进行了分析。鉴于纳米技术的应用在提高检测灵敏度、特异性以及准确率上具有优势,本文详细介绍了新型纳米传感器在SARS-CoV-2检测中的研究进展,包括表面增强拉曼基生物传感器、电化学生物传感器、磁纳米生物传感器以及比色生物传感器等,并探讨了纳米材料在新型生物传感器构建中的作用和挑战,为纳米材料研究人员开发各种类型的冠状病毒传感技术提供思路。     

2019新型冠状病毒的抗原抗体检测

2019新型冠状病毒(SARS-CoV-2)入侵人体引起急性呼吸道传染病,命名为2019冠状病毒病(COVID-19)。新冠病毒在全球范围传播对全球公共卫生安全构成了巨大的威胁,新冠病毒的检测对疫病诊断尤为重要。免疫分析技术作为核酸检测的辅助手段,主要用于对疑似病例和与感染者密切接触人员的筛查。免疫诊断技术包括抗体和抗原检测,通过检测感染部位或者血液样本中是否含有病毒本身的蛋白或是由病毒引起免疫反应而产生的抗体来判断是否携带病毒。对目前用于新冠病毒抗原和抗体检测的免疫分析方法着重进行了分析。     

Synthesis, characterization, and application of chiral ionic liquids and their polymers in micellar electrokinetic chromatography

Two amino acid-derived (leucinol and N-methylpyrrolidinol) chiral ionic liquids are synthesized and characterized in both monomeric and polymeric forms. Leucinol-based chiral cationic surfactant is a room-temperature ionic liquid, and pyrrolidinol-based chiral cationic surfactant melts at 30-35 degrees C to form an ionic liquid (IL). The monomeric and polymeric ILs are thoroughly characterized to determine critical micelle concentration, aggregation number, polarity, optical rotation, and partial specific volume. Herein, we present the first enantioseparation using chiral IL as a pseudostationary phase in capillary electrophoresis. Chiral separation of two acidic analytes, (+/-)-alpha-bromophenylacetic acid and (+/-)-2-(2-chlorophenoxy)propanoic acid (+/-)-(2-PPA) can be achieved with both monomers and polymers of undecenoxycarbonyl-L-pryrrolidinol bromide (L-UCPB) and undecenoxycarbonyl-L-leucinol bromide (L-UCLB) at 25 mM surfactant concentration using phosphate buffer at pH 7.50. The chiral recognition seems to be facilitated by the extent of interaction of the acidic analytes with the cationic headgroup of chiral selectors. Polysodium N-undecenoxycarbonyl-L-leucine sulfate (poly-L-SUCLS) and polysodium N-undecenoxycarbonyl-L-leucinate (poly-L-SUCL) were compared at high and low pH for the enantioseparation of (+/-)-(2-PPA). At pH 7.5, poly-L-SUCLS, poly-L-SUCL, and (+/-)-(2-PPA) are negatively charged resulting in no enantioseparation. However, chiral separation was observed for (+/-)-(2-PPA) using poly-L-SUCLS at low pH (pH 2.00) at which the analyte is neutral. The comparison of chiral separation of anionic and cationic surfactants demonstrates that the electrostatic interaction between the acidic analyte and cationic micelle plays a profound role in enantioseparation.     

Designing Non‐Native Iron‐Binding Site on a Protein Cage for Biological Synthesis of Nanoparticles

In biomineralization processes, a supramolecular organic structure is often used as a template for inorganic nanomaterial synthesis. The E2 protein cage derived from Geobacillus stearothermophilus pyruvate dehydrogenase and formed by the self‐assembly of 60 subunits, has been functionalized with non‐native iron‐mineralization capability by incorporating two types of iron‐binding peptides. The non‐native peptides introduced at the interior surface do not affect the self‐assembly of E2 protein subunits. In contrast to the wild‐type, the engineered E2 protein cages can serve as size‐ and shape‐constrained reactors for the synthesis of iron nanoparticles. Electrostatic interactions between anionic amino acids and cationic iron molecules drive the formation of iron oxide nanoparticles within the engineered E2 protein cages. The work expands the investigations on nanomaterial biosynthesis using engineered host‐guest encapsulation properties of protein cages.     

Molecular assembly and photoluminescence of novel rare earth/inorganic/polymeric hybrid materials with functional covalent linkages

In the context, organic polymeric precursor, polyethylene glycol (PEG) was firstly modified by inorganic component of 3-(triethoxysilyl)-propyl isocyanate (TEPIC) to form the inorganic/organic polymeric functional bridge precursor. Subsequently, the corresponding organic/inorganic molecular-based hybrids were assembled to behave the structural polymeric ligands with the two components equipped with covalent bonds. The coupling reagent part is a functional ureasils –NHC(=O)–O–group which is applied to coordinate to RE³⁺ and further formed Si–O backbones after hydrolysis and polycondensation processes. Furthermore, aromatic carboxylic acids (picolinic acid (HPIC), 2-chlorobenzoic acid (HCBA) and salicylic acid (HSAL)) were used as functional sensitized ligands to coordinate with RE³⁺(Eu³⁺, Tb³⁺ and Dy³⁺) and resulting in the quaternary rare earth/inorganic/organic polymeric hybrid materials with chemical bond (covalent bonds of –CO–NH– and Si–O, coordination bond of RE–O–C). Luminescence spectra were utilized to characterize the photophysical properties of the obtained hybrid material and the intramolecular energy transfer process took place within these molecular-based hybrids and characteristic emissions of RE³⁺ have been achieved.     

Biofunctional polystyrene derivatives exhibit a high affinity for the epidermal growth factor-receptor (EGF-R): Part I

Insoluble sulfamide of amino acid polystyrene derivatives interact with solubilized epidermal growth factor receptor (EGF-R). The choice of the different amino acids substituted on the polystyrene macromolecular chain is governed by the nature of the peptide involved in the binding of EGF on its receptor. This binding has a hydrophobic character with two affinity constants for EGF-R. Some of the amino acids involved in this fixation are known: Leu 44, Tyr 29, Leu 26, Ileu 23, Tyr 22, Val 19, Met 21. Therefore, statistic biofunctional polystyrene derivatives were synthesized with variable degrees of substitution by leucine and/or benzylamine or tyrosine. The random substitution may lead to complex sites that would interact with EGF-R like EGF. Indeed, among the studied copolymers, sulfamide of leucine 15% and 44% or tyrosine (35%) polystyrene derivatives exhibit a strong affinity for high and/or low affinity solubilized EGF-R and could be held as EGF-like polymers (affinity constants ranging from 2×10⁹ to 2×10¹¹ m ^–1)This paper was originally accepted after the 1993 Conference of the European Society for Biomaterials     

Nanozyme-Based Colorimetric SARS-CoV-2 Nucleic Acid Detection by Naked Eye

Fluorescence-based PCR and other amplification methods have been used for SARS-CoV-2 diagnostics, however, it requires costly fluorescence detectors and probes limiting deploying large-scale screening. Here, a cut-price colorimetric method for SARS-CoV-2 RNA detection by iron manganese silicate nanozyme (IMSN) is established. IMSN catalyzes the oxidation of chromogenic substrates by its peroxidase (POD)-like activity, which is effectively inhibited by pyrophosphate ions (PPi). Due to the large number of PPi generated by amplification processes, SARS-CoV-2 RNA can be detected by a colorimetric readout visible to the naked eye, with the detection limit of 240 copies mL⁻¹. This conceptually new method has been successfully applied to correctly distinguish positive and negative oropharyngeal swab samples of COVID-19. Colorimetric assay provides a low-cost and instrumental-free solution for nucleic acid detection, which holds great potential for facilitating virus surveillance.     

Interfacially organized DNA/polycation complexes: a route to new planar polymeric and composite nanostructures

Effects of nano-scale supramolecular organization and patterning in amphiphilic polycation monolayer formed by poly-4-vinilpyridine with 16% cetylpyridinium groups and in novel planar DNA/amphiphilic polycation complexes formed at the air-aqueous DNA solution interface and deposited on the solid substrates have been studied using AFM. Stable ordered quasi-crystalline planar polymeric monolayer structures were formed by amphiphilic polycation molecules. Extended net-like and quasi-circular toroidal condensed conformations of deposited planar DNA/amphiphilic polycation complexes were obtained in dependence on the amphiphilic polycation Langmuir monolayer state during the DNA binding. Those monolayer and multilayer DNA/polycation complex Langmuir–Blodgett films were used as templates and nanoreactors for generation of inorganic nanostructures. As a result, ultrathin polymeric nanocomposite films with integrated DNA building blocks and inorganic semiconductor (CdS) and iron oxide nanoparticle quasi-linear arrays or aggregates (nanorods) were formed successfully and characterized by TEM. The data obtained give evidence for effectiveness of the monolayer techniques for study mechanisms of DNA structural transformations caused by complexation with cationic compounds and demonstrate its perspectives for creation of new planar DNA-based self-organized stable polymeric complex nanostructures and nanocomposites with nano-scale structural ordering.     

Molecular dynamics simulations of the adsorption of amino acids on the hydroxyapatite {100}-water interface

The understanding of interfaces and interaction of organic molecules and inorganic materials are the important issues in biomineralization. Experimentally, it has been found that amino acids (AA) can regulate the morphology of hydroxyapatite (HAP) crystals significantly. In this study, molecular dynamics simulation is employed to investigate the detailed adsorption behavior of polar, ionic, and hydrophobic AA on the {100} face of HAP at the atomic level. The results indicate that various AA are adsorbed on the HAP crystal surface mainly by amino and carboxylate groups at the specific sites. Multiple interaction points are found for polar and ionic AA. The adsorbed AA molecules occupy the Ca and P sites of the HAP surfaces which may inhibit and regulate the HAP growth. The adsorbed amino acid layer can also change the interfacial hydration layer and influence the transportation of ions in and out of HAP, which may be another strategy of biological control in biomineralization.     

藏药牦牛血粉饮片中氨基酸和无机元素测定

为建立藏药牦牛血粉饮片中氨基酸和无机元素的定性和定量分析方法,试验采用高效液相色谱-柱后衍生法对牦牛血粉中游离氨基酸进行测定:离子交换柱(2.5 mm×150 mm,6μm),检测波长为570 nm、440 nm,测试方法为单点矫正法;采用微波消解-ICP-MS对牦牛血粉中无机元素进行测定:测定模式为碰撞反应模式,碰撞气(He)流量5 mL/min。数据采集模式:跳峰扫描,采样深度8.0 mm,重复扫描3次。结果表明:牦牛血粉中含有一定量的游离氨基酸,其中包括8种人体必须氨基酸。无机元素以Al、Na、Mg、K、Ca、Fe为主,还含有V、Cr、Mn、Zn、Co、Ni、Cu、Se等人体所需微量元素,各无机元素均在浓度考察范围内,线性关系良好(r^2>0.9984),加样回收率在99.2%~108.4%之间。该研究初步明确藏药牦牛血粉饮片中氨基酸和无机元素的组成,方法准确高效,为综合评价藏药牦牛血粉饮片的质量提供科学依据和方法参考。     

Influence of the substitution of β-cyclodextrins by cationic groups on the complexation of organic anions

The inclusion complexation of the organic anion, dansyl-acid, by cationic derivatives of β-cyclodextrin has been investigated. A series of cationic β-cyclodextrins with various positive charge has been synthesized by selective functionalization of the primary face of β-cyclodextrin with amino groups. The complexes were of the 1:1 stoichiometry; the stability constants (K₁₁) have been evaluated from UV–Vis measurements by application of the Benesi–Hildebrand equation. The presence of amino groups increased the complexation ability. β-cyclodextrin fully substituted at the primary face with amino groups showed the strongest inclusion binding ability towards the dansyl-acid guest. The enhanced complexation for anions was ascribed to the cationic amino groups. A simple thermodynamic model of the electrostatic contribution to the complexation is presented.