International Journal of Peptide Research and Therapeutics
·
2024
·Vol. 30
·期 5
·1-13
·
IF 2
Liu Ziyang,Wei Yuping,Zhang Man,Zhu Xingyan,Liu Kun
Angiotensin-converting enzyme-2 (ACE2) is a important cell surface receptor of SARS-CoV-2 S protein. The initial stage of SARS-COV-2 cell infection involves the binding of the S protein to ACE2. Hence, this work presents an innovative strategy to designing ACE2-based peptide inhibitors by considering the surface property and morphology of the S protein RBD. The aim is to develop a short peptide inhibitor that can effectively inhibit S protein-ACE2 interaction Through computational analysis and molecular simulation, the surface properties and morphology of S protein receptor-binding structural domain (RBD) were investigated, while the key residues of ACE2 ligand-binding structural domain (LBD) were identified based on their contributions and non-covalent interactions. Then, peptide inhibitors, consisting of ACE2 key residues, were developed by fitting to the surface characteristics and topographical features of the S protein RBD. Molecular simulation showed that two novel short peptides, IEPFF (I5) and WIEPFF (W6) had high affinity for S protein RBD but a low affinity for the cell membrane. Cellular adsorption studies demonstrated that both I5 and W6 effectively blocked ACE2-S protein binding without significant cytotoxicity. Flow cytometry analysis revealed that both I5 and W6 effectively inhibited S protein binding to the ACE2, resulting in a significant reduction (75 and 79%, respectively) in fluorescence intensity after 30 min of incubation at a concentration of 200 μM. Both I5 and W6 were excellent potential anti SARS-COV-2 drugs. This work provides an innovative perspective for the development of functional peptides for the prevention and management of SARS-COV-2.
研究领域:
生物化学
·
分子生物学
·
病毒学
·
药学
·
计算生物学
✓ 已验证
产品关联
DOI
高影响因子
Gut Microbes
·
2022
·
IF 9.434
Liqiu Jia,Shufeng Weng,Jing Wu,Xiangxiang Tian,Yifan Zhang,Xuyang Wang,Jing Wang,Dongmei Yan,Wanhai Wang,Fang Fang,Zhaoqin Zhu,Chao Qiu,Wenhong Zhang,Ying Xu,Yanmin Wan
The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.
研究领域:
免疫学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Yansheng Liu,Yongquan Wei,Guofu Wang,Xiaobo Jia,Jin Zhou,Hongqi Li,Haixin Chang,Zhaoxu Li
Surface-enhanced Raman scattering (SERS) spectroscopy plays an important role in enabling high-precision detection and non-invasive diagnostics. Periodic metallic nanostructures with strong electromagnetic fields and tunable localized surface plasmon resonance can achieve high SERS sensitivity, but fabricating such nanostructures remains a challenge. In this work, the anodic aluminum oxide (AAO) nanocavity template-assisted process of fabricating periodic nanostructures with modulating morphologies from Ag nanoclaws (AgNCWs) to Ag nanocones (AgNCEs) is proposed. The morphologies-related SERS performances of nanostructures are analyzed by using rhodamine 6 g (R6G) as a probe molecule and the optimized AgNCEs possess a limit of detection (LOD) of 1 × 10 −9 M. A sandwich strategy is applied to detect SARS-CoV-2 S protein in phosphate-buffered saline (PBS) and pharyngeal swab solution (PSS). The ACE2-modified AgNCEs (ACE2/AgNCEs) structure is applied to bind to the SARS-CoV-2 S protein. The 4-MBA and SARS-CoV-2 S antibody functionalized Au nanoparticles (AuNPs) are used as nanotags. By forming the ACE2/AgNCEs-SARS-CoV-2 S protein-nanotags sandwich structure, characteristic peak intensities of 1580 cm −1 are used as the report signal, and the LOD for SARS-CoV-2 S protein in PBS and PSS solution are 10 fg/mL.
研究领域:
生物医学工程
·
纳米技术
·
病毒学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS A-PHYSICAL
·
2024
·
IF 4.1
Jiaping Yang,Junpeng Deng,Yansheng Liu,Zhenle Qin,Jin Zhou,Xiaobo Jia,Guofu Wang,Yuqiang Weng,Feng Ling,Bin Zhou
Developing an efficient and sensitive method for detecting the coronavirus disease (COVID-19) is crucial. In this study, a phase-dependent SPR biosensor has been developed to detect the SARS-CoV-2 S protein with high sensitivity. The phase shifts of the SPR spectral interferogram are extracted using the windowed Fourier transform (WFT) method. The summation of the phase shifts of the prominent frequency, which make up the SPR spectral interferogram, is used as a numerical index to reflect the “negative” or “positive” results. The SARS-CoV-2 S protein antibody is modified onto an Au film, which serves as a sensing surface when detecting the SARS-CoV-2 S protein. The SARS-CoV-2 S protein antibody functionalized Au nanoparticles are used to form a (anti-S@AuNPs)-(SARS-CoV-2 S protein)-(Au film) sandwich structure, which reduces the SPR detection limitation to 1 ag/mL. An external laser is then used to induce the localized surface plasmon resonance (LSPR) between the AuNPs and the Au film in the sandwich structure, enhancing the detecting sensitivity by 357 %. This study provides a label-free method for detecting the SARS-CoV-2 S protein with low concentrations, indicating its potential in detecting the SARS-CoV-2 virus and viral disease diagnosis.
研究领域:
生物传感器技术
·
病毒学
·
医学诊断
✓ 已验证
产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Yansheng Liu,Haonan Hu,Xiaobo Jia,Jin Zhou,Hongli Li,Xiaohong Wang,Shaohui Zhang,Haixin Chang,Fuchong Li,Guofu Wang
This study reported a sandwich SERS structure in detecting SARS-CoV-2 spike protein (SARS-CoV-2 S protein) with high performance. The periodic Ag nanoarrays (AgNAs) functionalized with angiotensin-converting enzyme 2 (ACE2) were utilized as the bottom structure to specifically bound to the SARS-CoV-2 S protein. A complex of SARS-CoV-2 S protein antibody and 4-mercaptobenzoic acid (4-Mba) modified Au nanoparticles (AuNPs@4-Mba@Antibody) were used as nanotags and top SERS enhancing structures. By utilized the “hot spots” in parallel and perpendicular directions, the SERS signals of the 4-Mba as reporters were largely enhanced. By modulated the diameters and the heights of the AgNAs, the SERS performance of the sandwich structures was optimized by using R6G as a stand analyst with limits of detection (LOD) of 1 × 10 −9 M. By applied the optimized sandwich structures in detecting SARS-CoV-2 S protein in phosphate buffered saline (PBS) and pharyngeal swabs solution (PSS), the proposed sandwich structure illustrates a high performance, and the LODs were 0.1 fg mL −1 and 1 fg mL −1 , respectively. This study presented an efficient way to construct a sandwich SERS structure in directly detecting SARS-CoV-2 S protein and this method illustrates a good potential in viral detection.
研究领域:
生物医学工程
·
病毒学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Yi Liu,Huanjiao Weng,Zhiwei Chen,Ming Zong,Shubin Fang,Zili Wang,Shaohua He,Yangming Wu,Jizhen Lin,Shangyuan Feng,Duo Lin
The Omicron variants of SARS-CoV-2 have been spreading globally and has never disappeared from our sight, indicating that its coexistence with humans has become a fact, and monitoring its evolution and spread remains a current task. Although polymerase chain reaction (PCR) is the most commonly used virus detection method, it requires labor-intensive and time-consuming procedures in a laboratory setting. Herein, a multichannel nanoplasmonic sensing chip based on surface enhanced Raman spectroscopy (SERS) was developed for detecting N and S proteins, as well as IgG and IgM, related to SARS-CoV-2 Omicron variants. Through a self-screening process, specific antibodies for on-site and rapid identification of important variants of concerns (VoCs) were obtained, and their binding was confirmed by protein structure analysis. The use of these S protein specific antibodies can accurately identify Omicron VoCs (BA. 5, BF.7，XBB.1.5) with the detection limit (LoD) at 0.16 pg/mL. Then, the proposed SERS array chip was integrated with a hand-held Raman spectrometer to successfully detect the Omicron subvariants in real saliva samples within only 20 minutes, greatly reducing the detection time of PCR. This sensing technology will provide a powerful and rapid point-of-care testing (POCT) method for virus diagnosis, subtype identification, and post infection antibody level monitoring.
研究领域:
生物医学工程
·
分析化学
·
病毒学
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 13
·3022
·
IF 4.2
Yuping Wei,Ziyang Liu,Man Zhang,Xingyan Zhu,Qiuhong Niu
Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 μM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2.
研究领域:
药理学
·
病毒学
·
分子生物学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yaqin Zhang,Yingjie Cheng,Chenfei Zhao,Jianai Chen,Zhina Wu,Jiasi Wang,Di Wang
Simultaneous analysis of multiple protein and nucleic acid biomarkers in a single clinical sample can yield clinically valuable results for diagnosing, surveillance, and managing various diseases. However, the current diagnostic platforms depend largely on protein- or nucleic acid-independent assay, which is time-consuming and laborious. Here, we propose a novel assay termed MCD assay that can simultaneously detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene RNA and SARS-CoV-2 S protein. This assay was based on magnetic separation technology, combined with the clustered regularly interspaced palindromic repeats (CRISPR) /CRISPR-associated proteins (Cas) system for accessible point-of-care detection of nucleic acids and proteins. The assay could recognize target molecules through nucleic acid hybridization or antigen–antibody reactions and integrated with the CRISPR/Cas-based enzymatic detection; the lateral flow test strips enabled visualization of the assay results. The limit of detection of MCD was 1000 copies/μL for viral nucleic acid and 10 pg/mL for viral protein. The combined evaluation of multiple biomarkers from diverse pathways can enhance the accuracy and specificity of disease diagnosis. It is also crucial to use a single platform for detecting biomarkers across various dimensions to evaluate and manage major diseases.
研究领域:
分子生物学
·
医学诊断
·
生物技术
·
病毒学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Baochao Fan,Jun Gu,Bin Deng,Weilu Guo,Shuaifeng Zhang,Li Li,Bin Li
The COVID-19 pandemic continues to spread worldwide. To protect and control the spread of SARS-CoV-2, varieties of subunit vaccines based on spike (S) proteins have been approved for human applications. Here, we report a new subunit vaccine design strategy that functions as both an antigen carrier and an adjuvant in immunization to elicit high-level immune responses. The complex of 2-hydroxypropyl-trimethylammonium chloride chitosan and amylose entangles Au nanoparticles (HTCC/amylose/AuNPs) forming 40 nm nanocarriers with a positive charge. The obtained positively charged nanoparticles reveal many merits, including the larger S protein loading capacity in PBS buffer, higher cellular uptake ability, and lower cell cytotoxicity, supporting their potential as safe vaccine nanocarriers. Two functionalized nanoparticle subunit vaccines are prepared via loading full-length S proteins derived from SARS-CoV-2 variants. In mice, both prepared vaccines elicit high specific IgG antibodies, neutralize antibodies, and immunoglobulin IgG1 and IgG2a. The prepared vaccines also elicit robust T- and B-cell immune responses and increase CD19+ B cells, CD11C+ dendritic cells, and CD11B+ macrophages at the alveoli and bronchi of the immunized mice. Furthermore, the results of skin safety tests and histological observation of organs indicated in vivo safety of HTCC/amylose/AuNP-based vaccines. Summarily, our prepared HTCC/amylose/AuNP have significant potential as general vaccine carriers for the delivery of different antigens with potent immune stimulation.
研究领域:
纳米技术
·
免疫学
·
病毒学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）