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TALANTA · 2023 · IF 6.1

PdPtRu trimetallic nanozymes and application to electrochemical immunosensor for sensitive SARS-COV-2 antigen detection

Ying Li,Jian Xue,Rongjun Yu,Siling Chen,Xiangyu Deng,Anyi Chen,Jingfu Qiu

Herein, a ternary PdPtRu nanodendrite as novel trimetallic nanozyme was reported, which possessed excellent peroxidase-like activity as well as electro-catalytic activity on account of the synergistic effect between the three metals. Based on the excellent electro-catalytic activity of trimetallic PdPtRu nanozyme toward the reduction of H 2 O 2 , the trimetallic nanozyme was applied to construct a brief electrochemical immunosensor for SARS-COV-2 antigen detection. Concretely, trimetallic PdPtRu nanodendrite was used to modify electrode surface, which not only generated high reduction current of H 2 O 2 for signal amplification, but also provided massive active sites for capture antibody (Ab 1 ) immobilization to construct immunosensor. In the presence of target SARS-COV-2 antigen, SiO 2 nanosphere labeled detection antibody (Ab 2 ) composites were introduced on the electrode surface according sandwich immuno-reaction. Due to the inhibitory effect of SiO 2 nanosphere on the current signal, the current signal was decreased with the increasing target SARS-COV-2 antigen concentration. As a result, the proposed electrochemical immunosensor presented sensitive detection of SARS-COV-2 antigen with linear range from 1.0 pg/mL to 1.0 μg/mL and limit of detection down to 51.74 fg/mL. The proposed immunosensor provide a brief but sensitive antigen detection tool for rapid diagnosis of COVID-19.

CAS / MDL: 50-81-7 10049-07-7
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYST · 2023 ·Vol. 148 ·期 15 ·3603-3609 · IF 4.2

Post-synthetic modification-driven ZIF reconstruction and functionalization for efficient SARS-CoV-2 ECL detection

Ju-Zheng Wang,Yi-Xuan Li,Qiaoting Yang,Junji Li,Jérome Chauvin,Xue-Ji Zhang,Serge Cosnier,Robert S. Marks,Dan Shan

The emergence of novel pathogens, as well as their frequent variants, raises the significance of developing superior and versatile sensing materials and techniques. Herein, a post-modified zeolitic imidazolate framework (pm-ZIF) was synthesized by using ZIF-67 as a parent MOF, and zinc(II) meso-tetra (4-carboxyphenyl) porphine (ZnTCPP) as a successive exchange ligand. Due to the preservation of the tetrahedral Co–N4 units from the ZIF precursor and the introduced porphyrin luminophores, this hybrid material pm-ZIF/P(Zn) enables the linear electrochemiluminescence (ECL) signal conversion of the target DNA concentration. An efficient biosensor that can be used to quantitatively detect SARS-CoV-2 was therefore constructed. The linear range of the sensor was 10−12–10−8 M, with a limit of detection (LOD) reaching 158 pM. Compared with the traditional amplification-based methods, the duration time of our method is significantly shortened and the quantitation of the SARS-Cov-2 RdRp gene can be completed within twenty minutes at room temperature.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

Functionalized protein microparticles targeting hACE2 as a novel preventive strategy for SARS-CoV-2 infection

Yujia Li,Yike Huang,Kehui Zhu,Xiaoqiong Duan,Shilin Li,Min Xu,Chunhui Yang,Jiaxin Liu,Hans Bäumler,Pin Yu,He Xie,Bin Li,Ye Cao,Limin Chen

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), resulting in a serious burden on public health and social economy worldwide. SARS-CoV-2 infection is mainly initialized in the nasopharyngeal cavity through the binding of viral spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) receptors which are widely expressed in many human cells. Thus, blockade of the interaction between viral S protein and hACE2 receptor in the primary entry site is a promising prevention strategy for the management of COVID-19. Here we showed protein microparticles (PMPs) decorated with hACE2 could bind and neutralize SARS-CoV-2 S protein-expressing pseudovirus (PSV) and protect host cells from infection in vitro. In the hACE2 transgenic mouse model, administration of intranasal spray with hACE2-decorated PMPs markedly decreased the viral load of SARS-CoV-2 in the lungs though the inflammation was not attenuated significantly. Our results provided evidence for developing functionalized PMPs as a potential strategy for preventing emerging air-borne infectious pathogens, such as SARS-CoV-2 infection.

CAS / MDL: 111-30-8
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Foods · 2022 ·Vol. 11 ·期 18 ·2865 · IF 5.561

A Sulfated Abalone Polysaccharide Inhibited SARS-CoV-2 Infection of Vero E6 Cells In Vitro

Jinghe Sun,Shuang Song,Chunqing Ai,Beiwei Zhu,Jingfeng Yang

Sulfate polysaccharides, such as heparin sulfate, have been found to have inhibitory activity against SARS-CoV-2. An abalone polysaccharide, AGSP, was deeply sulfate modified using the chlorosulfonic acid/pyridine method, yielding S-AGSP. AGSP and S-AGSP inhibitions of SARS-CoV-2 infection of Vero E6 cells were tested in vitro. The interference of AGSP or S-AGSP on the binding interaction between the SARS-CoV-2 spike protein and angiotensin-converting enzyme was tested using a biolayer interferometry assay. Results showed that S-AGSP, above a concentration of 1.87 µg/mL, significantly inhibited SARS-CoV-2 infection of Vero E6 cells. Compared with AGSP, S-AGSP obviously weakened the affinity between the SARS-CoV-2 spike protein and ACE2. The polysaccharide’s sulfate content played a vital role in influencing the binding affinity of spike protein to ACE2. Therefore, S-AGSP has potential as a COVID-19 competitive inhibitor as well as a candidate to be repurposed as a prophylactic COVID-19 therapeutic.Keywords:sulfated;polysaccharide;SARS-CoV-2;biolayer interferometry;ACE2

CAS / MDL: 631-61-8
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Biosensors-Basel · 2022 ·Vol. 12 ·期 2 ·103 · IF 5.743

Latex Microsphere-Based Bicolor Immunochromatography for Qualitative Detection of Neutralizing Antibody against SARS-CoV-2

Zhanwei Liang,Tao Peng,Xueshima Jiao,Yang Zhao,Jie Xie,You Jiang,Bo Meng,Xiang Fang,Xiaoping Yu,Xinhua Dai

Neutralizing antibody (NAb) is a family of antibodies with special functions, which afford a degree of protection against infection and/or reduce the risk of clinically severe infection. Receptor binding domain (RBD) in the spike protein of SARS-CoV-2, a portion of the S1 subunit, can stimulate the immune system to produce NAb after infection and vaccination. The detection of NAb against SARS-CoV-2 is a simple and direct approach for evaluating a vaccine’s effectiveness. In this study, a direct, rapid, and point-of-care bicolor lateral flow immunoassay (LFIA) was developed for NAb against SARS-CoV-2 detection without sample pretreatment, and which was based on the principle of NAb-mediated blockage of the interaction between RBD and angiotensin-converting enzyme 2. In the bicolor LFIA, red and blue latex microspheres (LMs) were used to locate the test and control lines, leading to avoidance of erroneous interpretations of one-colored line results. Under the optimal conditions, NAb against SARS-CoV-2 detection carried out using the bicolor LFIA could be completed within 9 min, and the visible limit of detection was about 48 ng/mL. Thirteen serum samples were analyzed, and the results showed that the NAb levels in three positive serum samples were equal to, or higher than, 736 ng/mL. The LM-based bicolor LFIA allows one-step, rapid, convenient, inexpensive, and user-friendly determination of NAb against SARS-CoV-2 in serum.Keywords:neutralizing antibody;latex microspheres;lateral flow immunoassay;SARS-CoV-2;receptor binding domain

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELL · 2022 · IF 66.85

A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors

Liming Yan,Yucen Huang,Ji Ge,Zhenyu Liu,Pengchi Lu,Bo Huang,Shan Gao,Junbo Wang,Liping Tan,Sihan Ye,Fengxi Yu,Weiqi Lan,Shiya Xu,Feng Zhou,Lei Shi,Luke W. Guddat,Yan Gao,Zihe Rao,Zhiyong Lou

Summary Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5′ end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown “Nuc-pocket” in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an “induce-and-lock” mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.

CAS / MDL: 7787-56-6
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Visual naked-eye detection of SARS-CoV-2 RNA based on covalent organic framework capsules

Minghui Wang,Yuxin Lin,Jianyang Lu,Zhaowei Sun,Ying Deng,Lei Wang,Yongxiang Yi,Jinlong Li,Jie Yang,Genxi Li

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted that new diagnosis technologies are crucial for controlling the spread of the disease. Especially in the resources-limit region, conveniently operated detection methods such as “naked-eye” detection are urgently required that no instrument is needed. Herein, we have designed a novel and facile strategy to fabricate covalent organic framework (COF) capsules, which can be utilized to establish a new colorimetric assay for naked-eye detection of SARS-CoV-2 RNA. Specifically, we employ the digestible ZIF-90 as the sacrificial template to prepare the hollow COF capsules for horseradish peroxidase (HRP) encapsulation. The fabricated COF capsules can provide an appropriate microenvironment for the enzyme molecules, which may improve the conformational freedom of enzymes, enhance the mass transfer, and endow the enzyme with high environmental resistance. With such design, the proposed assay exhibits outstanding analytical performance for the detection of SARS-CoV-2 RNA in the linear range from 5 pM to 50 nM with a detection limit of 0.28 pM which can go parallel to qTR-PCR analysis. Our method also possesses excellent selectivity and reproducibility. Moreover, this method can also be served to analyze the clinical samples, and can successfully differentiate COVID-19 patients from healthy people, suggesting the promising potential in clinical diagnosis.

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Sensors & Diagnostics · 2022 ·Vol. 2 ·期 2 ·382-389 · IF 0

The design of anti-fouling and anti-hydrolysis cyclic peptides for accurate electrochemical antigen testing in human blood

Rui Han,Wenjie Hou,Yang Li,Min Chen,Caifeng Ding,Xiliang Luo

Antigen testing is an effective methodology for COVID-19 disease screening, and the receptor-binding domain of the SARS-CoV-2 spike glycoprotein (RBD) is recognized as a key biomarker for the diagnosis, treatment, and vaccination of COVID-19. However, the diagnosis of RBD directly in human biofluids remains a serious challenge owing to severe biological fouling in real samples. Herein, a sensitive electrochemical biosensor capable of detecting the RBD antigen in human blood was constructed based on a self-designed cyclic peptide. This cyclic peptide was designed to have good antifouling properties to resist nonspecific adsorption of proteins, etc. in blood, and the cyclic structure of the peptide was able to resist enzymatic hydrolysis by certain enzymes in blood, enhancing the stability of the peptide as well as the peptide-based biosensor. Compared with conventional linear peptides, the cyclic peptide possessed better antifouling properties and a much stronger anti-enzymatic hydrolysis ability. The electrochemical biosensor based on the cyclic peptide was capable of sensitively assaying RBD in the concentration range from 1.0 pg mL−1 to 100.0 ng mL−1, with a limit of detection of just 0.45 pg mL−1. Moreover, the biosensor was able to quantitatively detect RBD in real samples, and the results were more reliable than those measured with ELISA kits, especially in human blood with higher concentrations. This strategy of designing cyclic peptides for the construction of antifouling biosensors offered a new method for clinical detection of viral antigens in complex biological media like human blood.

研究领域: 生物化学 · 分析化学 · 生物医学工程 · 分子生物学
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Materials Today Bio · 2021 · IF 7.348

Liquid repellency enabled antipathogen coatings

W. Li,Y. Wang,X. Tang,T.T.T. Yuen,X. Han,J. Li,N. Huang,J.F.W. Chan,H. Chu,L. Wang

Currently, Coronavirus Disease 2019 (COVID-19)—a respiratory contagion spreading through expiratory droplets—has evolved into a global pandemic, severely impacting the public health. Importantly, the emerging of immune evasion SARS-CoV-2 variants and the limited effect of current antivirals against SARS-CoV-2 in clinical trials suggested that alternative strategies in addition to the conventional vaccines and antivirals are required to successfully control the COVID-19 pandemic. Here, we propose to use liquid-repellent coatings to prevent the spread of the disease in the absence of effective vaccines, antimicrobial agents, or therapeutics, wherein the deposition and penetration of pathogen droplets are prohibited. We use SARS-CoV-2 as a model pathogen and find that SARS-CoV-2 remnants are reduced by seven orders of magnitude on coated surfaces, yielding a repelling efficacy far outperforming the inactivation rate of disinfectants. The SARS-CoV-2 remnant scales exponentially with the liquid/solid adhesion, uncovering the mechanism and effective means for minimizing pathogen attachment. The antipathogen coating that both repels and inactivates pathogens is demonstrated by incorporating the super-liquid-repellent coating with antipathogen additives. Together with its versatility over a wide range of substrates and pathogens, the novel antipathogen coating is of considerable value for infection control in everyday life as well as during pandemics.

研究领域: 材料科学 · 生物医学工程 · 公共卫生
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Amplification-free detection method for pathogen nucleic acid based on manganese ion enhanced CRISPR system and magnetic enrichment

Dayong Li,Yanheng Yao,Wenting Cheng,Feifan Yin,Miao He,Yang Xiang

In this work, we constructed a manganese ion enhanced CRISPR fluorescence analysis platform based on magnetic separation technology and CRISPR/Cas12a system for the amplification-free detection of SARS-CoV-2 RNA. Firstly, nucleic acid functionalized magnetic beads and dual-function signal probes were used to identify conserved sequences of target RNA at the same time, and then the target was captured and separated by magnetic enrichment. The dual-function signal probe is used to bridge the recognition of the target and the output of the fluorescence signal. And the CRISPR activation sequence on the signal probe is used to initiate the downstream CRISPR/Cas12a fluorescence system to generate fluorescent signals. In this method, we used manganese ions to replace the traditional magnesium ions to assist the CRISPR/Cas12a system, which significantly enhanced the analysis effect. Moreover, we designed a variety of signal probes for different regions of the target RNA to further improve the signal intensity. This method can accurately detect the target RNA within 45 minutes, and can effectively identify the positive cases of COVID-19 infection in clinical throat swab samples, which has great potential for clinical application.

研究领域: 分子生物学 · 医学诊断 · 生物化学
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Advanced Optical Materials · 2024 · IF 8

Highly Absorbing Monolayer MoS2 for a Large Reflection Phase Modulation

Yingying Wang,Zhonglin Li,Xianglin Li,Kangyu Gao,Zhixiong Yin,Wenjun Liu,Bo Zhong,Guangfeng Kan,Xiaofei Wang,Jie Jiang,Zexiang Shen

Manipulation of wavefront lies at the core of next-generation information technologies. Compared to metal and dielectric metasurfaces, atomic 2D materials exhibit excellent prospects toward fulfilling ultra-thin thickness requirements in flat optics in wavefront shaping, with thickness much smaller than those of traditional bulky devices. However, phase manipulation by light propagating through atomic 2D materials is suppressed due to its sub-nanometer thickness. Here, an approach is reported to realize reflection phase singularities by establishing a zero-reflection point in a monolayer MoS 2 -based multilayer system, which broadens topological study beyond polarization singularity. This is achieved through the creation of a multilayer Fabry-Perot-type interference, and a pronounced phase change in the reflected light is realized due to the high absorption of monolayer MoS 2 in the studied wavelength range. As an application, a rapid, sensitive, and label-free detection of SARS-CoV-2 (2019-nCov) antigen is demonstrated with a detection limit of 10 −12 M L −1 (62 pg ml −1 ) by using monolayer MoS 2 based optical biosensor. In addition to offering a comprehensive study in phase singularity, efficient wavefront engineering based on the reflective system using materials is presented with atomic thickness which may greatly simplify optical architecture in flat optics, and promote its development toward compactness and integrated functions.

研究领域: 光学 · 生物医学工程 · 纳米技术 · 材料科学
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Cell Reports · 2026 ·Vol. 45 ·期 7 · IF 7.7

Type I unconventional protein secretion of the SARS-CoV-2 nucleocapsid protein promotes inflammatory cytokine release

Liwei Zheng,Minghui Li,Weilin Gu,Jing Zhao,Bei Jiang,Qianqian Jiang,Kun Liu,Yu Guo,Ran Xu,Xin Liu,Ting Zhang,Danli Yang,Sidi Yang,Lihong Liu,Qingquan Liu,Lin Wang,Sujun Zheng,Fengmin Lu,Xiangmei Chen

SARS-CoV-2 infection remains a global health threat, yet its pathogenic mechanisms are incompletely understood. Here, we show that viral nucleocapsid protein (NP) is detectable in the serum of patients with SARS-CoV-2 infection independently of viral RNA. Using virus-like particle (VLP) systems and in vitro infection models, we demonstrate that NP is secreted in a vesicle-free form via type I unconventional protein secretion (UPS) pathway. This process is regulated by NP phosphorylation and oligomerization, coordinated by viral structural proteins, and dependent on membrane components including heparan sulfate proteoglycans (HSPGs) and phosphatidylinositol 4,5-bisphosphate (PI (4,5) P 2 ). Secreted NP is preferentially taken up by granulocytes and induces the release of inflammatory cytokines, including IL-6 and TNF-α. Our findings shed a light on the secretion mechanism of this pro-inflammatory NP, highlighting it as a potential therapeutic target for COVID-related systemic inflammation.

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