Signal Transduction and Targeted Therapy
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2022
·Vol. 7
·期 1
·1-10
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IF 38.104
Wu Jiajing,Nie Jianhui,Zhang Li,Song Hao,An Yimeng,Liang Ziteng,Yang Jing,Ding Ruxia,Liu Shuo,Li Qianqian,Li Tao,Cui Zhimin,Zhang Mengyi,He Peng,Wang Youchun,Qu Xiaowang,Hu Zhongyu,Wang Qihui,Huang Weijin
Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.
研究领域:
病毒学
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免疫学
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流行病学
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DOI
PubMed
高影响因子
Natural Product Communications
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2025
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IF 1.4
Yongxia Shi,Xiaoning Sun,Zhaoxia Yu,Dalan Dai,Hongyu Guo,Lijuan Mei,Jun Dai,Lei Jiang
ObjectiveBergenia purpurascens, a medicinal herb indigenous to southwestern China, has garnered interest for its potential therapeutic properties. This study investigates the herb's water extract's capacity to interfere with the interaction between the COVID-19 S1 Receptor Binding Domain (RBD) and the ACE2 receptor, a critical step in the virus's infection process.MethodsQuality standards for the Bergenia purpurascens extract were established to ensure consistency. The extract's efficacy was assessed using a Vero-E6 cell infection model to inhibit live virus infection of the COVID-19 XBB1.5 variant. Surface Plasmon Resonance (SPR) was employed to explore the mechanism of action. The extract's composition was further analyzed using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS), with active compounds identified through a combination of in silico screening and actual activity testing.ResultsThe water extract of Bergenia purpurascens demonstrated significant inhibitory activity against the COVID-19 XBB1.5 variant, with stability and high potency, reflected by an IC50 value of 0.037 mg/mL. The selectivity index for the antiviral effect is approximately 9. The extract's composition was predominantly Phenylpropanoids and Carbohydrates, accounting for over 60% of the total. Interestingly, a majority of the high-content compounds were inactive, while the low-content compounds, exemplified by Ellagic acid, showed synergistic activity. The extract's inhibitory mechanism was characterized as a non-specific inhibition of ACE2 with a steady-state binding affinity (KD) of 7.9 × 10−7 M.ConclusionsThe study concludes that the water extract of Bergenia purpurascens is a promising, cost-effective non-specific ACE2 inhibitor with potential applications in COVID-19 therapy. The identification of active compounds and the elucidation of its inhibitory mechanism provide a foundation for further research and development of this traditional medicinal herb in combating viral infections.
研究领域:
药理学
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病毒学
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分子生物学
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DOI
高影响因子
Molecular Biomedicine
·
2025
·Vol. 6
·期 1
·1-14
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IF 10.1
Ao Danyi,Peng Dandan,He Cai,Ye Chunjun,Hong Weiqi,Huang Xiya,Lu Yishan,Shi Jie,Zhang Yu,Liu Jian,Wei Xiawei,Wei Yuquan
Despite the declared end of the COVID-19 pandemic, SARS-CoV-2 continues to evolve, with emerging JN.1-derived subvariants (e.g., KP.2, KP.3) compromising the efficacy of current XBB.1.5-based vaccines. To address this, we developed an mRNA vaccine encoding the full-length spike protein of JN.1, incorporating GSAS and 2P mutations and encapsulated in lipid nanoparticles (LNPs). The JN.1-mRNA vaccine elicited robust humoral and cellular immune responses in mice, including high JN.1-specific IgG titers, cross-neutralizing antibodies, and increased T follicular helper (Tfh) cells, germinal center (GC) B cells, and T cell cytokines. Importantly, immunity persisted for up to six months and induced RBD-specific long-lived plasma cells. We also compared the immune responses induced by homologous and heterologous vaccination regimens, and our results demonstrated that the heterologous regimen—combining JN.1-mRNA with a recombinant protein vaccine (RBD JN.1 -HR)—induced stronger responses. These findings highlight the JN.1-mRNA vaccine constitutes an effective prophylactic approach against JN.1-related variants, as it induces potent neutralizing antibody responses across all tested lineages. This enhanced immunogenicity is expected to significantly reduce hospitalization rates and mitigate post-COVID complications associated with JN.1 and KP.3 infections. This study emphasizes the need for timely vaccine updates and the adaptability of mRNA vaccines in addressing emerging pathogens, providing a framework for combating future infectious diseases. Collectively, these results offer critical insights for vaccine design and public health strategies in response to emerging SARS-CoV-2 variants.
研究领域:
病毒学
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免疫学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
LUMINESCENCE
·
2024
·Vol. 39
·期 1
·e4675
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IF 3.2
Gerile Oudeng,Junguo Ni,Hao Wu,Honglian Wu,Mo Yang,Chunyi Wen,Yuanwei Wang,Hui Tan
The coronavirus disease-2019 pandemic reflects the underdevelopment of point-of-care diagnostic technology. Nuclei acid (NA) detection is the “gold standard” method for the early diagnosis of the B.1.1.529 (Omicron) variant of severe acute respiratory syndrome-coronavirus disease-2. Polymerase chain reaction is the main method for NA detection but requires considerable manpower and sample processing taking ≥ 3 h. To simplify the operation processes and reduce the detection time, exonuclease III (Exo III)-aided MoS 2 /AIE nanoprobes were developed for rapid and sensitive detection of the oligonucleotides of Omicron. Molybdenum disulfide (MoS 2 ) nanosheets with excellent optical absorbance and distinguishable affinity to single-strand and duplex DNAs were applied as quenchers, and aggregation-induced emission (AIE) molecules with high luminous efficiency were designed as donor in fluorescence resonance energy transfer-based nanoprobes. Exo III with catalytic capability was used for signal amplification to increase the sensitivity of detection. The composite nanoprobes detected the mutated nucleocapsid (N)-gene and spike (S)-gene oligonucleotides of Omicron within 40 min with a limit of detection of 4.7 pM, and showed great potential for application in community medicine.
研究领域:
生物医学工程
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分子生物学
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病毒学
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2023
·
IF 8.9
Chenglong Lin,Zhenzhen Liu,Fanghao Fang,Shuai Zhao,Yanyan Li,Meimei Xu,Yusi Peng,Hongyou Chen,Fang Yuan,Wanju Zhang,Xi Zhang,Zheng Teng,Rui Xiao,Yong Yang
The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for rapid and accurate viral detection at the point-of-care testing (POCT). Compared with nucleic acid detection, lateral flow immunoassay (LFIA) is a rapid and flexible method for POCT detection. However, the sensitivity of LFIA limits its use for early identification of patients with COVID-19. Here, an innovative surface-enhanced Raman scattering (SERS)-LFIA platform based on two-dimensional black phosphorus decorated with Ag nanoparticles as important antigen-capturing and Raman-signal-amplification unit was developed for detection of SARS-CoV-2 variants within 5–20 min. The novel SERS-LFIA platform realized a limit of detection of 0.5 pg/mL and 100 copies/mL for N protein and SARS-CoV-2, demonstrating 1000 times more sensitivity than the commercial LFIA strips. It could reliably detect seven different SARS-CoV-2 variants with cycle threshold (Ct) < 38, with sensitivity and specificity of 97 and 100%, respectively, exhibiting the same sensitivity with q-PCR. Furthermore, the detection results for 48 SARS-CoV-2-positive nasopharyngeal swabs (Ct = 19.8–38.95) and 96 negative nasopharyngeal swabs proved the reliability of the strips in clinical application. The method also had good specificity in double-blind experiments involving several other coronaviruses, respiratory viruses, and respiratory medications. The results showed that the innovative SERS-LFIA platform is expected to be the next-generation antigen detection technology. The inexpensive amplification-free assay combines the advantages of rapid low-cost POCT and highly sensitive nucleic acid detection, and it is suitable for rapid detection of SARS-CoV-2 variants and other pathogens. Thus, it could replace existing antigens and nucleic acids to some extent.
研究领域:
医学诊断
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病毒学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
·
2021
·Vol. 31
·期 10
·1047-1060
·
IF 25.617
Hu Wei,Zhang Yong,Fei Panyu,Zhang Tongtong,Yao Danmei,Gao Yufei,Liu Jia,Chen Hui,Lu Qiao,Mudianto Tenny,Zhang Xinrui,Xiao Chuxuan,Ye Yang,Sun Qiming,Zhang Jing,Xie Qi,Wang Pei-Hui,Wang Jun,Li Zhenhai,Lou Jizhong,Chen Wei
The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike’s S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Mechanistically, such mechano-activation is fulfilled by force-induced opening and rotation of spike’s receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding, up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application, and subsequently by force-accelerated S1/S2 detachment which is up to ~10 3 times faster than that in the no-force condition. Interestingly, the SARS2-S D614G mutant, a more infectious variant, shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment. We also reveal that an anti-S1/S2 non-RBD-blocking antibody that was derived from convalescent COVID-19 patients with potent neutralizing capability can reduce S1/S2 detachment by 3 × 10 6 times under force. Our study sheds light on the mechano-chemistry of spike activation and on developing a non-RBD-blocking but S1/S2-locking therapeutic strategy to prevent SARS2 invasion.
研究领域:
病毒学
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分子生物学
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生物物理学
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产品关联
DOI
PubMed
高影响因子
TALANTA
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2022
·
IF 6.556
Bin Yang,Xiaowei Zeng,Jin Zhang,Jilie Kong,Xueen Fang
Delta (B.1.617.2), a highly infectious variant of SARS-CoV-2, has been sweeping the world, and threatening the safety of human life seriously. It is urgent to develop a highly selective and sensitive assay to accurately identify the SARS-CoV-2 variant Delta. In this work, we constructed a graphene/CRISPR-dCas9 electrochemical biosensor to accurately identify SARS-CoV-2 variant Delta, where the signal was further amplified by embedded electrochemical probe [Ru(phen) 2 dppz]BF 4 . This detection assay could be finished within 47 min totally, with the detection limit of 1.2 pM and good reproducibility with a C·V.% of 2.48% (n = 5). And the biosensor could selectively identify Delta among SARS-CoV-2 and other variants, including Alpha, Beta, Gamma. This assay was further validated by 26 real clinical samples, showing 100% clinical sensitivity and 100% clinical specificity, which provides a new direction for identifying other SARS-CoV-2 variants in the future.
研究领域:
生物技术
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电化学
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分子生物学
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病毒学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2025
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IF 6
Jiahai Wang,Jianji Zhu,Yunhui Li,Cenlin Gui,Baian Zhu,Zhuobin Zhu,Daqi Chen
Enhancing the signal-to-noise ratio (SNR) has long been a focus of research in the development of nanopore sensors. Herein, a 3D DNA origami cube with adjustable rigidity that exhibits exceptional selectivity and an ultra-high SNR exceeding 100 is designed and optimized. The assembly of this 3D DNA origami cube relies on a single scaffold strand derived from target DNA/RNA, as well as multiple staple strands. This construction process ensures that the cube only forms in the presence of the target DNA/RNA, thereby providing a highly sensitive and specific detection strategy. Without any intermediate steps, DNA amplicons amplified from a plasmid containing the S gene of the Omicron variant of SARS-CoV-2 were successfully transformed into 3D DNA origami cubes in the presence of staple strands in a one-pot reaction process. Nanopore counting of 3D DNA origami cubes, instead of the direct detection of the target gene, significantly ameliorates the interference effect from non-target subjects possessing a similar size and charge. This approach features an ultra-low detection limit of 50 aM, with a broad detection range from 50 aM to 50 pM, even in commercial buffers that contain large amounts of enzymes, stable proteins, and other non-target DNA sequences. Moreover, the DNA origami cube has a thermal stability of up to 70°C, which allows it to be used in a wide range of scenarios, including harsh conditions. We aim to extend this approach to detect many other targets and to integrate it into broader diagnostic toolkits. Nevertheless, given space constraints, not all possible applications could be thoroughly explored within this study.
研究领域:
生物物理学
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纳米技术
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分子诊断学
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产品关联
DOI
PubMed
高影响因子
Cell Discovery
·
2023
·Vol. 9
·期 1
·1-15
·
IF 33.5
Ai Liangxia,Li Yafei,Zhou Li,Yao Wenrong,Zhang Hao,Hu Zhaoyu,Han Jinyu,Wang Weijie,Wu Junmiao,Xu Pan,Wang Ruiyue,Li Zhangyi,Li Zhouwang,Wei Chengliang,Liang Jianqun,Chen Haobo,Yang Zhimiao,Guo Ming,Huang Zhixiang,Wang Xin,Zhang Zhen,Xiang Wenjie,Sun Dazheng,Xu Lianqiang,Huang Meiyan,Lv Bin,Peng Peiqi,Zhang Shangfeng,Ji Xuhao,Luo Huiyi,Chen Nanping,Chen Jianping,Lan Ke,Hu Yong
Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.
研究领域:
病毒学
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免疫学
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药学
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生物技术
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Jingwang Qin,Xiangdong Tian,Siying Liu,Zhengxia Yang,Dawei Shi,Sihong Xu,Yun Zhang
The spread of COVID-19 over the past three years is largely due to the continuous mutation of the virus, which has significantly impeded global efforts to prevent and control this epidemic. Specifically, mutations in the amino acid sequence of the surface spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have directly impacted its biological functions, leading to enhanced transmission and triggering an immune escape effect. Therefore, prompt identification of these mutations is crucial for formulating targeted treatment plans and implementing precise prevention and control measures. In this study, the label-free surface-enhanced Raman scattering (SERS) technology combined with machine learning (ML) algorithms provide a potential solution for accurate identification of SARS-CoV-2 variants. We establish a SERS spectral database of SARS-CoV-2 variants and demonstrate that a diagnostic classifier using a logistic regression (LR) algorithm can provide accurate results within 10 min. Our classifier achieves 100% accuracy for Beta (B.1.351/501Y.V2), Delta (B.1.617), Wuhan (COVID-19) and Omicron (BA.1) variants. In addition, our method achieves 100% accuracy in blind tests of positive and negative human nasal swabs based on the LR model. This method enables detection and classification of variants in complex biological samples. Therefore, ML-based SERS technology is expected to accurately discriminate various SARS-CoV-2 variants and may be used for rapid diagnosis and therapeutic decision-making.
研究领域:
病毒学
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生物医学工程
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机器学习
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分析化学
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公共卫生
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2023
·
IF 8.9
Yun Zhang,Bo Chen,Duo Chen,Yiming Wang,Qingqing Lu,Jie Tan,Long Chen,Liping Zhou,Weihong Tan,Yanbing Yang,Quan Yuan
The large-scale pandemic and fast evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have triggered an urgent need for an efficient and sensitive on-site nucleic acid testing method with single-nucleotide polymorphism (SNP) identification capability. Here, we report a multiplexed electrical detection assay based on a paperclip-shaped nucleic acid probe (PNprobe) functionalized field-effect transistor (FET) biosensor for highly sensitive and specific detection and discrimination of SARS-CoV-2 variants. The three-stem structure of the PNprobe significantly amplifies the thermodynamic stability difference between variant RNAs that differ in a single-nucleotide mutation. With the assistance of combinatorial FET detection channels, the assay realizes simultaneously the detection and identification of key mutations of seven SARS-CoV-2 variants, including nucleotide substitutions and deletions at single-nucleotide resolution within 15 min. For 70 simulated throat swab samples, the multiplexed electrical detection assay shows an identification accuracy of 97.1% for the discrimination of SARS-CoV-2 variants. Our designed multiplexed electrical detection assay with SNP identification capability provides an efficient tool to achieve scalable pandemic screening.
研究领域:
生物医学工程
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分子生物学
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病毒学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2023
·
IF 8.8
Yang Yi,Wenzhe Li,Kefang Liu,Heng Xue,Rong Yu,Meng Zhang,Yang-Oujie Bao,Xinyuan Lai,Jingjing Fan,Yuxi Huang,Jing Wang,Xiaomeng Shi,Junhua Li,Hongping Wei,Kuanhui Xiang,Linjie Li,Rong Zhang,Xin Zhao,Xue Qiao,Hang Yang,Min Ye
Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC 50 of 1.016 μM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
研究领域:
病毒学
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药理学
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免疫学
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分子生物学
✓ 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）