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Virology Journal · 2025 ·Vol. 22 ·期 1 ·1-14 · IF 3.8

Identification of Co-29, a 5-cyano-2-thiacetyl aromatic pyrimidinone, as a potential inhibitor targeting the RdRp of norovirus

Liu Xianglan,Hu Jiaming,Wu Jiarui,Tian Yiru,Wang Jinbo,Wu Chunyan,Chen Qingfeng,Krall Leonard,He Yanping,Lu Qun

Background Human norovirus (HNV) is the predominant pathogen causing outbreaks of acute gastroenteritis globally. Despite significant efforts to combat norovirus infections, there is currently no FDA approved vaccine or antiviral drug available. Consequently, the development of effective antiviral agents is of critical importance. Methods and results In this study, a series of 41 5-cyano-2-thiacetyl aromatic pyrimidinone compounds were designed and synthesized. A cell viability-based screening for anti-murine norovirus (MNV) compounds was conducted, revealing that compound 29 (hereafter used as Co-29) exhibited antiviral activity against MNV. Co-29 demonstrated effective inhibition of MNV CW3 RNA replication, exhibiting an EC 50 of 58.22 μM. An RdRp enzyme activity assay indicated that Co-29 directly inhibits RdRp activity to both MNV and HNV. Molecular docking studies suggested that Co-29 interacts with the palm region of RdRp via hydrogen bonding with specific residues, which are conserved in RdRps across MNV and HNV norovirus variants. Conclusions In conclusion, our study suggests that the newly synthesized Co-29 may serve as a potential antiviral candidate or lead compound for future studies.

CAS / MDL: 36051-31-7
研究领域: 病毒学 · 药物化学 · 分子生物学
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Frontiers in Nutrition · 2022 · IF 6.59

Determination of Antiviral Mechanism of Centenarian Gut-Derived Limosilactobacillus fermentum Against Norovirus

Ying Li,Junshan Gao,Liang Xue,Yanyan Shang,Weicheng Cai,Xinqiang Xie,Tong Jiang,Huizhen Chen,Jumei Zhang,Juan Wang,Moutong Chen,Yu Ding,Qingping Wu

Although noroviruses are the causative agents of most non-bacterial foodborne disease outbreaks, effective antivirals are currently unavailable. Certain probiotic strains have been reported as active antivirals for norovirus infections, but their mechanisms have not been fully elucidated. Herein, we examined the antiviral potential of 122 lactic acid bacteria isolates against murine norovirus (MNV), a human norovirus surrogate. A centenarian gut-derived strain, Limosilactobacillus fermentum PV22, exhibited the strongest MNV antagonism and reduced the viral titer by 2.23 ± 0.38 (log-value) in 5 min with stable activity at 25°C ( P < 0.01). Genome mining revealed that its antiviral activity can be attributed to the synthesis of γ-aminobutyric acid, and this finding was experimentally verified. Furthermore, we demonstrated the safety of the isolate and its high intestinal colonization ability. In conclusion, we discovered a centenarian gut-derived L. fermentum strain with strong anti-norovirus activity and identified its antiviral metabolite. Our results will offer new solutions for the prevention and treatment of food-related norovirus infections.

CAS / MDL: 56-12-2
研究领域: 微生物学 · 病毒学 · 食品科学 · 益生菌研究 · 肠道微生物组
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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

A portable, one-tube CRISPR/Cas12a-based biosensor for sensitive and colorimetric detection of norovirus in foods without pre-amplification

Caihong Zhou,Jingjing Fan,Liangyuan Wang,Baoxue Gao,Chunhui Wei,Long Ma,Lijuan Yin

Norovirus (NoV) is a leading cause of nonbacterial acute gastroenteritis, primarily transmitted through contaminated food and water. Rapid, sensitive, and on-site detection is crucial for controlling NoV outbreaks and ensuring food safety. In this study, we developed a portable, one-tube CRISPR/Cas12a-driven colorimetric biosensor for the rapid and sensitive detection of NoV RNA without the need for pre-amplification. The biosensor integrates magnetic nanoprobes with gold nanoparticle (AuNP) bioprobes, connected via single-stranded DNA (ssDNA) linkers. Upon the specific recognition of NoV cDNA, the Cas12a protein’s trans -cleavage activity is activated, cleaving the ssDNA linkers and releasing AuNP bioprobes from the magnetic nanoprobes. This release results in a visually detectable red color change and enhanced UV–visible absorbance in the solution following magnetic separation. These changes can be easily detected using portable devices such as microplate readers or smartphones. This method achieves a detection limit of 10 copies/µL within 60 min, with no cross-reactivity from other viruses or bacteria. Validation using oyster samples showed perfect concordance with qPCR results. Designed for resource-limited settings, our biosensor can be adapted for detecting various pathogens by altering the target nucleic acids and crRNA sequences. This advancement offers significant potential for enhancing rapid diagnostics and outbreak management.

研究领域: 分子生物学 · 食品科学 · 诊断技术
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ACS Sensors · 2024 · IF 8.2

Self-Powered Immunoassay of Norovirus in Human Stools by π-Electron-Rich Homojunction for Enhanced Charge Transfer

Yun Chen,Yunfan Jia,Xingwang Zhu,Li Xu,Henan Li,Huaming Li

Norovirus (NoV) stands as a significant causative agent of nonbacterial acute gastroenteritis on a global scale, presenting a substantial threat to public health. Hence, the development of simple and rapid analytical techniques for NoV detection holds great importance in preventing and controlling the outbreak of the epidemic. In this work, a self-powered photoelectrochemical (PEC) immunosensor of NoV capsid protein (VP1) was proposed by the π-electron-rich carbon nitride homojunction (ER-CNH) as the photoanode. C4N2 ring derived from π-rich locust bean gum was introduced into the tri-s-triazine structure, creating a large π-delocalized conjugated carbon nitride homojunction. This strategy enhances the C/N atomic ratio, which widens light utilization, narrows the bandgap, and optimizes the electronic band structure of carbon nitride. By introduction of a π-rich conjugated structure, p-type domains were induced within n-type domains to build the internal electric field at the interface, thus forming a p–n homojunction to boost carrier separation and transfer. The ER-CNH photoanode exhibited excellent photoelectric performance and water oxidation capacity. Since VP1 inhibits the water oxidation of the ER-CNH photoanode, the open-circuit potential of the as-prepared PEC immunosensor system was reduced for detecting NoV VP1. The self-powered PEC immunosensor achieved a remarkably low detection limit (∼5 fg mL–1) and displayed high stability and applicability for actual stool samples. This research serves as a foundation concept for constructing immunosensors to detect other viruses and promotes the application of self-powered systems for life safety.

CAS / MDL: 9000-40-2 31175-20-9
研究领域: 生物医学工程 · 分析化学 · 公共卫生
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICA CHIMICA ACTA · 2025 · IF 6

A magnetic CRISPR/Cas12a-SERS nanobiosensor for amplification-free and ultrasensitive detection of norovirus in water and food samples

Caihong Zhou,Yongzhao Zhang,Xuejing Yang,Ziqian Zhao,Menglei Xia,Chunhui Wei,Qiankun Wu,Zisong Chang,Long Ma,Lijuan Yin

Background Norovirus (NoV) is the leading cause of foodborne disease outbreaks worldwide, typically spreading via contaminated food and water. Rapid, sensitive, and portable detection of NoV is crucial. Results Here, we presented a magnetic CRISPR/Cas12a-SERS nanobiosensor capable of detecting NoV with high sensitivity, accuracy, speed, and portability. In this nanobiosensor, SERS nanoprobes linked to magnetic nanoprobes via linker single-stranded DNAs (ssDNAs). The presence of NoV nucleic acid triggered Cas12a's trans -cleavage activity, degrading the linker ssDNA. After magnetic separation, the dissociated SERS nanoprobes were efficiently separated from the magnetic nanoprobes. This enhanced the SERS signal in the supernatant, detectable using a portable Raman spectrometer. The detection limit for NoV is 100 copies/mL within 60 min. The nanobiosensor was further assessed in real-world settings, demonstrating excellent sensitivity and selectivity for detecting trace NoV in complex food samples. Significance This approach not only broadens CRISPR-based pathogen detection but also provides a reliable tool for monitoring foodborne viruses. Its potential extends beyond NoV, promising enhanced surveillance of various pathogens in food safety, environmental monitoring, and public health sectors.

研究领域: 生物技术 · 食品安全 · 分子诊断
✓ 已验证 DOI PubMed 高影响因子
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BMC MICROBIOLOGY · 2021 ·Vol. 21 ·期 1 ·1-10 · IF 3.605

Broad-range and effective detection of human noroviruses by colloidal gold immunochromatographic assay based on the shell domain of the major capsid protein

Xu Meng,Lu Feifeng,Lyu Chenang,Wu Qingping,Zhang Jumei,Tian Peng,Xue Liang,Xu Ting,Wang Dapeng

Background Human noroviruses (HuNoVs) are a major cause of nonbacterial gastroenteritis in all age groups worldwide. HuNoVs can be detected in vitro using molecular assays such as RT-PCR and RT-qPCR. However, these molecular-based techniques require special equipment, unique reagents, experienced personnel, and extended time to obtain results. Besides, the diversity of viral genotypes is high. Therefore, methods that are rapid, broad-range and effective in the detection of HuNoVs are desiderated for screening the feces or vomit of infected people during outbreaks. Results In this study, a colloidal-gold-based immunochromatographic assay (ICA) was developed for effective detection of HuNoVs in clinical samples. Monoclonal antibodies (MAbs) against the shell (S) domain in the major capsid protein of HuNoVs were used in the ICA. The limitations of detection for HuNoVs in clinical samples were 1.2 × 10 6 genomic copies per gram of stool sample (gc/g) and 4.4 × 10 5 gc/g for genogroup I and II (GI and GII) HuNoVs, respectively. A total of 122 clinical samples were tested for HuNoVs by ICA and compared against RT-qPCR. The relative sensitivity, specificity and agreement of ICA was 84.2% (95% CI: 83.6–84.8%), 100.0% (95% CI: 98.5–100.0%) and 87.7% (95% CI: 85.6–89.8%), respectively. No cross-reaction with other common enteric viruses or bacteria was observed. The ICA detected a broad range of genotypes, including GI.1, GI.3, GI.4, GI.6, GI.14, GII.2, GII.3, GII.4, GII.6, GII.13, and GII.17 HuNoVs. Conclusions This study demonstrates that ICA targeting the S domain of VP1 is a promising candidate for effectively identifying the different genotypes of HuNoVs in clinical samples with high sensitivity and specificity.

研究领域: 医学诊断 · 病毒学 · 分子生物学
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Sensors & Diagnostics · 2024 · IF 3.5

Detection of SARS-CoV-2 and noroviruses in cold-chain food samples using aptamer-functionalized graphene field-effect transistors

Qingliu Wu,Songjia Luo,Lu Wang,Baolei Dong,Hao Qu,Lei Zheng

Given the susceptibility of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and Norovirus (NoV) to survive in cold chain food, thereby posing significant public health risks, we present a novel approach for biosensor development utilizing a graphene field-effect transistor (GFET) modified with nucleic acid aptamers. The biosensor’s innovative design incorporates 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE) as a coupling agent to facilitate the attachment of nucleic acid aptamers onto channel graphene. This modification induces a redistribution of charge on the graphene surface, resulting in a shift of the Dirac point upon target capture by the nucleic acid aptamer. Through this pioneering methodology, we successfully engineered SARS-CoV-2 GFET and NoV GFET biosensors capable of detecting trace amounts of SARS-CoV-2 and norovirus within a rapid 5-minute timeframe, showcasing detection limits of 33 fg/mL and 6.17 pg/mL, respectively. Subsequently, we applied these sensors to detect SARS-CoV-2 in frozen meat and norovirus in shellfish, yielding promising results with excellent specificity and stability. This groundbreaking sensing mechanism holds significant promise for the detection of foodborne viruses across a diverse range of food samples.

研究领域: 生物传感器技术 · 病毒检测 · 食品安全
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2019 · IF 3.571

Characterization of a Histo-Blood Group Antigen-like Substance in Romaine Lettuce That Contributes to Human Norovirus Attachment

Zilei Zhang,Danlei Liu,Qingping Wu,Yu Lu,Peng Tian,Zhongfu Wang,Dapeng Wang

Human noroviruses (HuNoVs) are among the main pathogens causing acute nonbacterial gastroenteritis. Histo-blood group antigens (HBGAs) are widely accepted receptors for HuNoV specific binding. HBGA-like substances in produce are also considered as the critical ligands for capture of HuNoVs. However, the composition of viral ligands from food substrates remains unknown. In this study, an oligosaccharide (H2N2F2) was captured and isolated from romaine lettuce extract by a bacterial surface display system. Using electrospray ionization mass spectrometry and tandem mass spectrometry, it was shown that H2N2F2 was most likely to be a chimera of type A, H, and Lewis a HBGAs. The composition was consistent with our ELISA results using a panel of monoclonal antibodies against HBGAs. Our results revealed a possible interaction mechanism between HuNoVs and romaine lettuce. Better understanding of the interaction of HuNoVs with easily contaminated produce will ultimately aid in the control of and reduction in disease outbreaks.

CAS / MDL: 9016-45-9
研究领域: 病毒学 · 食品科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2021 · IF 7.46

3D-architectured aptasensor for ultrasensitive electrochemical detection of norovirus based on phosphorene-gold nanocomposites

Hai Jiang,Zhikang Sun,Cheng Zhang,Xuan Weng

A 3D electrochemical aptasensor was constructed for sensitive detection of norovirus, featuring in a highly sensitive and movable spherical working electrode (WE) decorated with phosphorene-gold nanocomposites (BP-AuNCs) and screen-printed electrodes on fabric. The BP-AuNCs were prepared via the in situ reduction of phosphorene nanosheets (BPNSs) on chloroauric acid (HAuCl 4 ), representing a simple, low-cost and mass-producible process. The design of the movable spherical WE facilitated the increase of surface area, ease of sampling and avoidance of cross-contamination. The critical design parameters of the 3D electrochemical aptasensor, including the concentration of immobilized aptamer and reaction time, were adjusted to yield tunable ranges for the assay dynamic range and limit of detection (LOD) for the recombinant norovirus-like particles. Under optimum conditions, the 3D electrochemical aptasensor revealed a limit of detection (LOD) of 0.28 ng/mL with a linear range between 1 ng/mL and 10 µg/mL. The relative standard deviation (RSD) of repeatability and reproducibility of the aptasensor were 2.29% and 3.03%, respectively. It was applied to determine norovirus spiked oyster samples and the recovery was found between 97.2% and 103.7%. In addition, it exhibited good stability, repeatability and selectivity . We believe that the proposed 3D electrochemical aptasensor provides a facile, low-cost paradigm for sensitive and selective detection of norovirus and would be of great potential in the realm of food safety and clinical diagnosis.

研究领域: 生物传感技术 · 食品安全 · 临床诊断
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Microorganisms · 2025 ·Vol. 14 ·期 1 ·11 · IF 4.2

Superior RdRp Function Drives the Dominance of Prevalent GI.3 Norovirus Lineages

Qianxin Lu,Huisha Du,Xin Jiang,Bingwen Zeng,Tianhui Li,Ying-Chun Dai

The GI.3 norovirus is the most detected and recombinant-rich genotype within genogroup I, yet the mechanistic basis for its epidemiological success remains poorly understood. This study integrates Bayesian evolutionary analysis with in vitro enzymology to investigate the link between RdRp function and the evolutionary dynamics of GI.3 NoV. We analyzed 831 GI.3 sequences, finding that prevalent strains (GI.3[P3] and GI.3[P13]) exhibited significantly higher evolutionary rates in both the RdRp and VP1 genes than non-prevalent strains (GI.3[P10] and GI.3[P14]). While the RdRp gene displayed a strong molecular clock signal, the VP1 gene’s evolution was more complex, showing cluster-specific trends. Functionally, the RdRps from prevalent strains demonstrated superior enzymatic activity and substrate affinity (Km: GI.3[P13] = 0.092 mM; GI.3[P3] = 0.176 mM) compared to non-prevalent strains (Km: GI.3[P14] = 0.273 mM). Notably, GI.3 RdRp required higher manganese ion concentrations for optimal activity than previously reported for GII strains, suggesting a potential biochemical constraint. Our findings demonstrate a clear correlation between RdRp enzymatic efficiency, evolutionary rate, and strain prevalence. We propose that a highly active RdRp may potentially accelerate VP1 evolution and confer a replicative advantage, underpinning the dominance of specific GI.3 lineages. This work provides crucial experimental evidence linking viral polymerase function to evolutionary and epidemiological outcomes.

✓ 已验证 DOI PubMed 高影响因子
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SENSORS · 2018 ·Vol. 18 ·期 9 ·2980 · IF 2.475

Development of CdSe–ZnO Flower-Rod Core-Shell Structure Based Photoelectrochemical Biosensor for Detection of Norovirous RNA

Zhizhong Han,Qinghua Weng,Chaofan Lin,Jinquan Yi,Jie Kang

In this work, the CdSe–ZnO flower-rod core-shell structure (CSZFRs) was prepared by ion-exchange method. The surface of CSZFRs was modified by 3-mercaptopropionic acid (MPA), and then the DNA probe was immobilized on the surface via chemical bond between -NH2of DNA probe and -COOH of MPA. Finally, the target norovirous (NV) RNA was combined with the probe according to the principle of complementary base pairing, resulting in a decrease of the photocurrent. The results show that the absorbance spectrum of visible light is enhanced for CSZFRs compared with pure ZnO. Under visible light irradiation, the photocurrent of CSZFRs is up to 0.1 mA, which can improve the sensitivity of the photoelectrochemical (PEC) biosensor. In the measurement range of 0–5.10 nM, the measured concentrations (c) have a good linear relationship with the output photocurrent of the biosensor. The linear regression equation is expressed asI= 0.03256 − 0.0033c(R2= 0.99, S/N = 3) with a detection limit of 0.50 nM. Therefore, this work realizes a rapid and sensitive method for the detection of NV RNA.Keywords:CdSe–ZnO flower-rod;photoelectrochemical biosensor;norovirous RNA;ion-exchange method

研究领域: 材料科学 · 生物化学 · 分析化学 · 病毒学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Science and Human Wellness · 2023 · IF 7

One stone two birds: electrochemical and colorimetric dual-mode biosensor based on copper peroxide/covalent organic framework nanocomposite for ultrasensentive norovirus detection

Guobao Ning,Quanmei Duan,Huan Liang,Huifang Liu,Min Zhou,Chunlan Chen,Chong Zhang,Hui Zhao,Canpeng Li

Norovirus (NoV) is regarded as one of the most common causes of foodborne diarrhea in the world. It is urgent to identify the pathogenic microorganism of the diarrhea in short time. In this work, we developed an electrochemical and colorimetric dual-mode detection for NoV based on the excellent dual catalytic properties of copper peroxide/COF-NH 2 nanocomposite (CuO 2 @COF-NH 2 ). For the colorimetric detection, NoV can be directly detected by the naked eye based on CuO 2 @COF-NH 2 as a laccase-like nonazyme using “peptide-NoV-antibody” recognition mode. The colorimetric assay displayed a wide and quality linear detection range from 1 copy/mL to 5000 copies/mL of NoV with a low limit of detection (LOD) of 0.125 copy/mL. For the electrochemical detection of NoV, CuO 2 @COF-NH 2 showed an oxidation peak of copper ion from Cu + to Cu 2+ using “peptide-NoV-antibody” recognition mode. The electrochemical assay showed a linear detection range was 1 5000 copies/mL with a LOD of 0.152 copy/mL. It’s worthy to note that this assay does not need other electrical signal molecule, which provide the stable and sensitive electrochemial detection for NoV. The electrochemical and colorimetric dual-mode detection was used to detect NoV in foods and faceal samples, which has the potential for improving food safety and diagnosing of NoV-infected diarrhea.

研究领域: 生物传感器 · 食品安全 · 医学诊断 · 分析化学
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