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Measures of insulin resistance and beta cell function before and after treatment of HCV infection

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Virologica Sinica 2024年第4期39卷 667-674页

作者： Jizheng Chen Pan Qiu Tingfeng Zhao Haowei Jiang Kebinur Tursun Sulaiman Ksimu Xinwen Chen Qian Wang State Key laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510182China Jiangsu Province Key Lab of Human Functional Genomics Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing210029China State Key laboratory of virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China Guangzhou laboratory Guangzhou510005China The First Affiliated Hospital of Xinjiang Medical University Urumchi830054China

The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic ***,we evaluated indices ofβ-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DMin individuals with and without chronic hepatitis C(CHC),and the effects of antiviral treatments on these variables.A total of 153 noncirrhotic,non-fibrotic CHC patients with a BMIclinical manifestations and complications.

关键词： Hepatitis C virus(HCV) Type 2 diabetes(T2DM) Beta cell(β-cell) Insulin secretion

Extracellular Disintegration of Viral Proteins as an Innovative Strategy for Developing Broad-Spectrum Antivirals Against Coronavirus

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CCS Chemistry 2024年第2期6卷 487-496页

作者： Ke Sun Zhe Ding Xiaoying Jia Haonan Cheng Yingwen Li Yan Wu Zhuoyu Li Xiaohua Huang Fangxu Pu Entao Li Guiyou Wang Wei Wang Yun Ding Gary Wong Sandra Chiu Jiaming Lan Aiguo Hu Shanghai Key laboratory of Advanced Polymeric Materials School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237 CAS Key laboratory of Molecular virology&Immunology Chinese Academy of SciencesShanghai 200031 University of the Chinese Academy of Sciences Beijing 100049 State Key laboratory of virology Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071 Division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230027 Department of clinical laboratory The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has claimedmillions of lives and caused innumerable economic losses ***,state-of-the-art treatments still lag behind the continual emergence of new *** to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural ***,we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne(EDY)*** core EDY generates reactive radical species and causes significant damage to the spike protein of coronavirus,while the hyperanion groups ensure negligible cytotoxicity of the *** EDYs exhibit antiviral activity down to nanomolar concentrations,and the selectivity index of up to 20,000 against four kinds of human coronavirus,including the SARS-CoV-2 Omicron variant,suggesting the high potential of this new strategy in combating the COVID-19 pandemic and a future“disease X.”

关键词： enediyne broad spectrum antiviral protein disintegration coronavirus polyanions

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan Institute of virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key laboratory of virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key laboratory of Molecular virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State Key laboratory of virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University Key laboratory of Medical Molecular virology(MOE/MOH) Shanghai Medical CollegeFudan University laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

关键词：

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

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Biomedical and Environmental Sciences 2024年第4期37卷 387-398页

作者： ZHAO Zi Jin CHEN Xiao Ping HUA Shao Wei LI Feng Yu ZHAO Meng XING Chen Hao WANG Jie TIAN Feng Yu ZHANG Rui Qing LYU Xiao Na HAN Zhi Qiang WANG Yu Xin LI Hong Yi SHEN Xin Xin MA Xue Jun TIE Yan Qing Graduate School Hebei North UniversityZhangjiakou 075000HebeiChina Department of clinical laboratory Hebei General HospitalShijiazhuang 050051HebeiChina National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China Department of clinical laboratory Pathology Diagnostic Center Shiyan General HospitalShiyan 442000HubeiChina Graduate School Hebei Medical University Shijiazhuang 050031HebeiChina

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification *** study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with *** Recombinant plasmids were used to evaluate the assay *** blood influenza bacteria were used for the specific *** and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)*** analysis was used to evaluate the consistency between the two *** The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial *** M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

关键词： Staphylococcus aureus Pseudomonas aeruginosa Acinetobacter baumannii Human Mannan-binding lectin protein Bloodstream infection Recombinase-aided PCR assay Multiple detection

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1651-1664页

作者： Xiong Xie Qiaoshuai Lan Jinyi Zhao Sulin Zhang Lu Liu Yumin Zhang Wei Xu Maolin Shao Jingjing Peng Shuai Xia Yan Zhu Keke Zhang Xianglei Zhang Ruxue Zhang jian Li Wenhao Dai Zhen Ge Shulei Hu Changyue Yu Jiang Wang Dakota Ma Mingyue Zheng Haitao Yang Gengfu Xiao Zihe Rao Lu Lu Leike Zhang Fang Bai Yao Zhao Shibo Jiang Hong Liu Drug Discovery and Design Center State Key Laboratory of Drug ResearchCAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Key laboratory of Medical Molecular virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghai 200032China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key laboratory of virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China School of Chinese Materia Medica Nanjing University of Chinese Medicine138 Xian Lin RoadJiangsu 210023 NanjingChina School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China National clinical Research Center for Infectious Disease Shenzhen Third People's HospitalShenzhen 518112China

Respiratory disease caused by coronavirus infection remains a global health *** several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be ***-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging *** L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune ***,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and *** X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of *** showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various *** mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral ***,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in *** addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse *** 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute *** together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with anti

关键词： calpain overcome entrance

Epidemiological Characteristics of Dengue Fever-China,2005–2023

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China CDC weekly 2024年第41期6卷 1045-1048页

作者： Zhuowei Li Xiaoxia Huang Aqian Li Shanshan Du Guangxue He Jiandong Li National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases NHC Key Laboratory of BiosafetyNHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Diseases Control and PreventionBeijingChina

Introduction:The global incidence of dengue fever has increased significantly over the past two decades,and China faces a significant upward trend in dengue control ***:Data were obtained from China’s NNDRS from 2005 to *** regression software was used to analyze temporal trends,while SaTScan software was used to analyze spatial,seasonal,and spatiotemporal *** software was used to visualize ***:A total of 117,892 dengue cases were reported from 2005 to 2023,with significant fluctuation in annual reported *** was not endemic in *** outbreaks most likely occurred in the southwestern,southeastern coastal,and inland areas of *** outbreaks have occurred between June and November,generally peaking in September or October,around epidemiological week(EW)***:Dengue challenges in China are *** case monitoring,proactive control interventions,and staff mobilization should be implemented before June to ensure a timely response to autochthonous outbreaks.

关键词： inland likely southwestern

Risk of infection with arboviruses in a healthy population in Pakistan based on seroprevalence

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Virologica Sinica 2024年第3期39卷 369-377页

作者： Shengyao Chen Muhammad Saqib Hafiz Sajid Khan Yuan Bai Usman Ali Ashfaq Muhammad Khalid Mansoor Abulimti Moming Jing Liu Min Zhou Saifullah Khan Niazi Qiaoli Wu Awais-Ur-Rahman Sial Shuang Tang Muhammad Hassan Sarfraz Aneela Javed Sumreen Hayat Mohsin Khurshid Iahtasham Khan Muhammad Ammar Athar Zeeshan Taj Bo Zhang Fei Deng Ali Zohaib Shu Shen Key laboratory of virology and National Virus Resource Center Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China Faculty of Veterinary Science University of Agriculture FaisalabadFaisalabad 38040Pakistan The Children's Hospital Faisalabad 38000Pakistan Department of Bioinformatics and Biotechnology Government College University FaisalabadFaisalabad 38000Pakistan f Department of Microbiology Faculty of Veterinary and Animal SciencesThe Islamia University of BahawalpurBahawalpur 63100Pakistan Hubei Jiangxia laboratory Wuhan 430200China Key laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China Armed Forces Institute of Pathology(AFIP) Rawalpindi 46000Pakistan Department of clinical Studies Faculty of Veterinary&Animal SciencesPir Mehr Ali Shah Arid Agriculture UniversityRawalpindi 46300Pakistan Institute of Microbiology Government College University FaisalabadFaisalabad 38000Pakistan l Atta-ur-Rahman School of Applied Biosciences National University of Science and TechnologyIslamabad 44000Pakistan Department of clinical Sciences University of Veterinary and Animal SciencesLahore Sub-campusJhang 35200Pakistan Department of Molecular Pathology National Medical Center DHA Phase 1Karachi 75500Pakistan

Infectious diseases caused by arboviruses are a public health concern in ***,studies on data prevalence and threats posed by arboviruses are *** study investigated the seroprevalence of arboviruses in a healthy population in Pakistan,including severe fever with thrombocytopenia syndrome virus(SFTSV),Crimean-Congo hemorrhagic fever virus(CCHFV),Tamdy virus(TAMV),and Karshi virus(KSIV)based on a newly established luciferase immunoprecipitation system(LIPS)assays,and Zika virus(ZIKV)by enzyme-linked immunosorbent assays(ELISA).Neutralizing activities against these arboviruses were further examined from the antibody positive *** results showed that the seroprevalence of SFTSV,CCHFV,TAMV,KSIV,and ZIKV was 17.37%,7.58%,4.41%,1.10%,and 6.48%,respectively,and neutralizing to SFTSV(1.79%),CCHFV(2.62%),and ZIKV(0.69%)were identified,as well as to the SFTSV-related Guertu virus(GTV,0.83%).Risk factors associated with the incidence of exposure and levels of antibody response were ***,co-exposure to different arboviruses was demonstrated,as thirty-seven individuals were having antibodies against multiple viruses and thirteen showed neutralizing ***,individuals aged40 years,and outdoor workers had a high risk of exposure to *** these results reveal the substantial risks of infection with arboviruses in Pakistan,and indicate the threat from co-exposure to multiple *** findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan.

关键词： Arbovirus Pakistan Seroprevalence Tick-borne virus Mosquito-borne virus

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris Chun-Yiu Chan Qian Guo Jasper Fuk-Woo Chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng Chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen Wing-Ho Chu Wan-Mui Chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-Yun Wang Yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-Yung Yuen Shuofeng Yuan State Key laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China Department of Infectious Diseases and Microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China Centre for virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics