1.Research progress in vaccines of SARS-CoV-2.
Xinbin GE ; Qigan QU ; Zeguang WANG ; Shungeng ZHANG ; Yan CHI ; Chunhui SHAN ; Ruihan LIU ; Qing ZHAO
Chinese Journal of Cellular and Molecular Immunology 2023;39(10):946-951
Since the outbreak of corona virus disease 2019 (COVID-19), viral strains have mutated and evolved. Vaccine research is the most direct and effective way to control COVID-19. According to different production mechanisms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines included inactivated virus vaccine, live attenuated vaccine, mRNA vaccine, DNA vaccine, viral vector vaccine, virus-like particle vaccine and protein subunit vaccine. Among them, viral protein subunit vaccine has a wide application prospect due to its high safety and effectiveness. Viral nucleocapsid protein has high immunogenicity and low variability which could be a new direction for vaccine production. We summarized the current development of vaccine research by reviewing the current progress, vaccine safety and vaccine immune efficiency. It is hoped that the proposed possible development strategies could provide a reference for epidemic prevention work in future.
Humans
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SARS-CoV-2/genetics*
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COVID-19/prevention & control*
;
Protein Subunits
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Vaccines, DNA
;
Nucleocapsid Proteins
2.The two-stage interaction of Ebola virus VP40 with nucleoprotein results in a switch from viral RNA synthesis to virion assembly/budding.
Linjuan WU ; Dongning JIN ; Dan WANG ; Xuping JING ; Peng GONG ; Yali QIN ; Mingzhou CHEN
Protein & Cell 2022;13(2):120-140
Ebola virus (EBOV) is an enveloped negative-sense RNA virus and a member of the filovirus family. Nucleoprotein (NP) expression alone leads to the formation of inclusion bodies (IBs), which are critical for viral RNA synthesis. The matrix protein, VP40, not only plays a critical role in virus assembly/budding, but also can regulate transcription and replication of the viral genome. However, the molecular mechanism by which VP40 regulates viral RNA synthesis and virion assembly/budding is unknown. Here, we show that within IBs the N-terminus of NP recruits VP40 and is required for VLP-containing NP release. Furthermore, we find four point mutations (L692A, P697A, P698A and W699A) within the C-terminal hydrophobic core of NP result in a stronger VP40-NP interaction within IBs, sequestering VP40 within IBs, reducing VP40-VLP egress, abolishing the incorporation of NC-like structures into VP40-VLP, and inhibiting viral RNA synthesis, suggesting that the interaction of N-terminus of NP with VP40 induces a conformational change in the C-terminus of NP. Consequently, the C-terminal hydrophobic core of NP is exposed and binds VP40, thereby inhibiting RNA synthesis and initiating virion assembly/budding.
Ebolavirus/physiology*
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HEK293 Cells
;
HeLa Cells
;
Humans
;
Nucleocapsid Proteins/metabolism*
;
RNA, Viral/metabolism*
;
Viral Matrix Proteins/metabolism*
;
Virion/metabolism*
;
Virus Assembly
3.The nucleocapsid protein of rice stripe virus in cell nuclei of vector insect regulates viral replication.
Wan ZHAO ; Junjie ZHU ; Hong LU ; Jiaming ZHU ; Fei JIANG ; Wei WANG ; Lan LUO ; Le KANG ; Feng CUI
Protein & Cell 2022;13(5):360-378
Rice stripe virus (RSV) transmitted by the small brown planthopper causes severe rice yield losses in Asian countries. Although viral nuclear entry promotes viral replication in host cells, whether this phenomenon occurs in vector cells remains unknown. Therefore, in this study, we systematically evaluated the presence and roles of RSV in the nuclei of vector insect cells. We observed that the nucleocapsid protein (NP) and viral genomic RNAs were partially transported into vector cell nuclei by utilizing the importin α nuclear transport system. When blocking NP nuclear localization, cytoplasmic RSV accumulation significantly increased. In the vector cell nuclei, NP bound the transcription factor YY1 and affected its positive regulation to FAIM. Subsequently, decreased FAIM expression triggered an antiviral caspase-dependent apoptotic reaction. Our results reveal that viral nuclear entry induces completely different immune effects in vector and host cells, providing new insights into the balance between viral load and the immunity pressure in vector insects.
Animals
;
Cell Nucleus
;
Hemiptera/metabolism*
;
Insect Vectors/genetics*
;
Insecta
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Nucleocapsid Proteins/metabolism*
;
Oryza
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Plant Diseases
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Tenuivirus/metabolism*
;
Virus Replication
4.Virtual screening of active ingredients of traditional Chinese medicine in treating COVID-19 based on molecular docking and molecular dynamic simulation.
Minghao LIU ; Iqbal Khan FAEZ ; Yuqing XIAO ; Xu WANG ; Ziran HU ; Dakun LAI
Journal of Biomedical Engineering 2022;39(5):1005-1014
We aim to screen out the active components that may have therapeutic effect on coronavirus disease 2019 (COVID-19) from the severe and critical cases' prescriptions in the "Coronavirus Disease 2019 Diagnosis and Treatment Plan (Trial Ninth Edition)" issued by the National Health Commission of the People's Republic of China and explain its mechanism through the interactions with proteins. The ETCM database and SwissADME database were used to screen the active components contained in 25 traditional Chinese medicines in 3 prescriptions, and the PDB database was used to obtain the crystal structures of 4 proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular docking was performed using Autodock Vina and molecular dynamics simulations were performed using GROMACS. Binding energy results showed that 44 active ingredients including xambioona, gancaonin L, cynaroside, and baicalin showed good binding affinity with multiple targets of SARS-CoV-2, while molecular dynamics simulations analysis showed that xambioona bound more tightly to the nucleocapsid protein of SARS-CoV-2 and exerted a potent inhibitory effect. Modern technical methods are used to study the active components of traditional Chinese medicine and show that xambioona is an effective inhibitor of SARS-CoV-2 nucleocapsid protein, which provides a theoretical basis for the development of new anti-SARS-CoV-2 drugs and their treatment methods.
Humans
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SARS-CoV-2
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Molecular Docking Simulation
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Medicine, Chinese Traditional
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Molecular Dynamics Simulation
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Nucleocapsid Proteins
;
Antiviral Agents/pharmacology*
;
COVID-19 Drug Treatment
5.Seroprevalence of IgM and IgG Antibodies against SARS-CoV-2 in Asymptomatic People in Wuhan: Data from a General Hospital Near South China Seafood Wholesale Market during March to April in 2020.
Rui Jie LING ; Yi Han YU ; Jia Yu HE ; Ji Xian ZHANG ; Sha XU ; Ren Rong SUN ; Wang Cai ZHU ; Ming Feng CHEN ; Tao LI ; Hong Long JI ; Huan Qiang WANG
Biomedical and Environmental Sciences 2021;34(9):743-749
The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test,
Adolescent
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Adult
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Aged
;
Aged, 80 and over
;
Antibodies, Viral/blood*
;
COVID-19/immunology*
;
Carrier State/immunology*
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Child
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Child, Preschool
;
China/epidemiology*
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Coronavirus Nucleocapsid Proteins/immunology*
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Cross-Sectional Studies
;
Female
;
Humans
;
Immunoglobulin G/blood*
;
Immunoglobulin M/blood*
;
Male
;
Middle Aged
;
Occupations/classification*
;
Phosphoproteins/immunology*
;
SARS-CoV-2/immunology*
;
Seroepidemiologic Studies
;
Spike Glycoprotein, Coronavirus/immunology*
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Young Adult
6.Understanding the phase separation characteristics of nucleocapsid protein provides a new therapeutic opportunity against SARS-CoV-2.
Dan ZHAO ; Weifan XU ; Xiaofan ZHANG ; Xiaoting WANG ; Yiyue GE ; Enming YUAN ; Yuanpeng XIONG ; Shenyang WU ; Shuya LI ; Nian WU ; Tingzhong TIAN ; Xiaolong FENG ; Hantao SHU ; Peng LANG ; Jingxin LI ; Fengcai ZHU ; Xiaokun SHEN ; Haitao LI ; Pilong LI ; Jianyang ZENG
Protein & Cell 2021;12(9):734-740
7.Fecal Nucleic Acid Test as a Complementary Standard for Cured COVID-19 Patients.
Mei HAN ; Jing Bo ZOU ; Huan LI ; Xiao Yu WEI ; Song YANG ; Hui Zheng ZHANG ; Peng Sen WANG ; Qian QIU ; Le Le WANG ; Yao Kai CHEN ; Pin Liang PAN
Biomedical and Environmental Sciences 2020;33(12):935-939
Adolescent
;
Adult
;
Aged
;
COVID-19/virology*
;
COVID-19 Nucleic Acid Testing/methods*
;
Child
;
Coronavirus Nucleocapsid Proteins/genetics*
;
Feces/virology*
;
Female
;
Humans
;
Male
;
Middle Aged
;
Phosphoproteins/genetics*
;
RNA, Viral/genetics*
;
SARS-CoV-2/isolation & purification*
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Young Adult
8.Nucleocapsid protein from porcine epidemic diarrhea virus isolates can antagonize interferon-λ production by blocking the nuclear factor-κB nuclear translocation.
Ying SHAN ; Zi-Qi LIU ; Guo-Wei LI ; Cong CHEN ; Hao LUO ; Ya-Jie LIU ; Xun-Hui ZHUO ; Xing-Fen SHI ; Wei-Huan FANG ; Xiao-Liang LI
Journal of Zhejiang University. Science. B 2018;19(7):570-580
Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PEDV exhibits an obvious capacity for modulating interferon (IFN) signaling or expression. The newly discovered type III IFN, which plays a crucial role in antiviral immunity, has strong antiviral activity against PEDV proliferation in IPEC-J2 cells. In this study, we aimed to investigate the effect of PEDV nucleocapsid (N) protein on type III IFN-λ. We found that the N proteins of ten PEDV strains isolated between 2013 and 2017 from different local farms shared high nucleotide identities, while the N protein of the CV777 vaccine strain formed a monophyletic branch in the phylogenetic tree. The N protein of the epidemic strain could antagonize type III IFN, but not type I or type II IFN expression induced by polyinosinic-polycytidylic acid (poly(I:C)) in IPEC-J2 cells. Subsequently, we demonstrated that the inhibition of poly(I:C)-induced IFN-λ3 production by PEDV N protein was dependent on the blocking of nuclear factor-κB (NF-κB) nuclear translocation. These findings might help increase understanding of the pathogenesis of PEDV and its mechanisms for evading the host immune response.
Active Transport, Cell Nucleus
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Animals
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Coronavirus Infections
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immunology
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veterinary
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virology
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Genes, Viral
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Host-Pathogen Interactions
;
immunology
;
Interferons
;
antagonists & inhibitors
;
biosynthesis
;
genetics
;
Interleukins
;
antagonists & inhibitors
;
biosynthesis
;
genetics
;
NF-kappa B
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metabolism
;
Nucleocapsid Proteins
;
genetics
;
immunology
;
physiology
;
Porcine epidemic diarrhea virus
;
genetics
;
pathogenicity
;
physiology
;
Promoter Regions, Genetic
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Swine
;
Swine Diseases
;
immunology
;
virology
9.Evaluation of two different enzyme-linked immunosorbent assay for severe fever with thrombocytopenia syndrome virus diagnosis
Min Ah YU ; Hye Won JEONG ; Su Jin PARK ; Young Il KIM ; Hyeok Il KWON ; Eun Ha KIM ; Young Jae SI ; Kwang Min YU ; Norbert John ROBLES ; Hae Jung HAN ; Young Ki CHOI
Clinical and Experimental Vaccine Research 2018;7(1):82-86
To develop the large scale serological assay for severe fever with thrombocytopenia syndrome virus (SFTSV) infection, we evaluated two different enzyme-linked immunosorbent assay (ELISA) methods using nucleocapsid protein (NP) and Gn proteins of CB1 (genotype B) SFTSV strains. The NP-based ELISA tests showed more sensitive with broad cross-reactivity between two different genotype A and B strains compared with those of Gn-based ELISA tests. However, Gn-based ELISA showed more genotype specificity and specificity. These result suggested that NP-based ELISA test could be applicable for general sero-prevalence studies of SFTSV infections, while Gn-based ELISA could be applicable for a certain specific genotype sero-prevalence study.
Diagnosis
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Enzyme-Linked Immunosorbent Assay
;
Fever
;
Genotype
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Nucleocapsid Proteins
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Sensitivity and Specificity
;
Thrombocytopenia
10.An enhanced immunochromatographic strip test using colloidal gold nanoparticle-labeled dual-type N proteins for detection of antibodies to PRRS virus
Ji Eun YU ; In Ohk OUH ; Hyeonjeong KANG ; Hye young LEE ; Kwang Myun CHEONG ; In Soo CHO ; Sang Ho CHA
Journal of Veterinary Science 2018;19(4):519-527
Porcine reproductive and respiratory syndrome (PRRS) is recognized as one of the most important infectious diseases causing serious economic loss in the swine industry worldwide. Due to its increasing genetic diversity, a rapid and accurate diagnosis is critical for PRRS control. The immunochromatographic strip test (ICST) is a rapid and convenient type of immunoassay. In this study, an on-site immunochromatographic assay-based diagnostic method was developed for detection of PRRS virus (PRRSV)-specific antibodies. The method utilized colloidal gold nanoparticle-labeled dual-type nucleocapsid proteins encoded by open reading frame 7. We evaluated 991 field samples from pig farms and 66 serum samples from experimentally PRRSV-inoculated pigs. Based on true PRRSV-specific antibody-positive or
Agriculture
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Antibodies
;
Colloids
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Communicable Diseases
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Diagnosis
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Enzyme-Linked Immunosorbent Assay
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Fluorescent Antibody Technique
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Genetic Variation
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Gold Colloid
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Immunoassay
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Immunochromatography
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Immunoglobulin M
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Methods
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Nucleocapsid Proteins
;
Open Reading Frames
;
Porcine Reproductive and Respiratory Syndrome
;
Porcine respiratory and reproductive syndrome virus
;
Sensitivity and Specificity
;
Swine

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