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Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants

Virologica Sinica 2021年第5期36卷 934-947页

作者： Yuanyuan Qu Xueyan Zhang Meiyu Wang Lina Sun Yongzhong Jiang Cheng Li Wei Wu Zhen Chen Qiangling Yin Xiaolin Jiang Yang Liu Chuan Li Jiandong Li Tianlei Ying Dexin Li Faxian Zhan Youchun Wang Wuxiang Guan Shiwen Wang Mifang Liang State Key Laboratory for Molecular Virology and Genetic Engineering National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Center for Emerging Infectious diseases Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071HubeiChina division of hiv/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China Hubei Provincial Center for disease Control and Prevention Wuhan 430065China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesFudan UniversityShanghai 200032China Shandong Center for disease Control and Prevention Jinan 250014China University of Chinese Academy of Sciences Beijing 100049China Peking Union Medical College Beijing 100730China

Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic *** this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display *** them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co *** structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding *** the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co ***,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain *** unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral *** findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.

关键词： Antibody cocktail Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Broad neutralization SARS-CoV-2 variants Angiotensin-converting enzyme 2(ACE2)

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Spatial epidemiology of diabetes: Methods and insights

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World Journal of Diabetes 2021年第7期12卷 1042-1056页

作者： Diego F Cuadros Jingjing Li Godfrey Musuka Susanne F Awad Geography and Geographic Information Systems University of CincinnatiCincinnatiOH 45221United States Urban Health Collaborative Drexel UniversityPhiladelphiaPA 19104United States ICAP Columbia UniversityHarare 00000Zimbabwe Infectious disease Epidemiology Group Weill Cornell Medicine–QatarCornell UniversityDoha 24144Qatar World Health Organization Collaborating Centre for disease Epidemiology Analytics on hiv/AIDS Sexually Transmitted Infectionsand Viral HepatitisWeill Cornell Medicine–QatarCornell UniversityDoha 24144Qatar Department of Population Health Sciences Weill Cornell MedicineCornell UniversityNew YorkNY 10044United States

Diabetes mellitus(DM)is a growing epidemic with global *** is estimated that in 2019,463 million adults aged 20-79 years were living with *** latest evidence shows that DM continues to be a significant global health challenge and is likely to continue to grow substantially in the next decades,which would have major implications for healthcare expenditures,particularly in developing ***,new conceptual and methodological approaches to tackle the epidemic are long *** epidemiology has been a successful approach to control infectious disease epidemics like malaria and human immunodeficiency *** implementation of this approach has been expanded to include the study of non-communicable diseases like cancer and cardiovascular *** this review,we discussed the implementation and use of spatial epidemiology and Geographic Information Systems to the study of *** reviewed several spatial methods used to understand the spatial structure of the disease and identify the potential geographical drivers of the spatial distribution of ***,we discussed the use of spatial epidemiology on the design and implementation of geographically targeted prevention and treatment interventions against DM.

关键词： Diabetes mellitus Spatial epidemiology Risk factors Spatial statistics disease mapping

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Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1357-1368页

作者： Miao-Miao Zhao Wei-Li Yang Fang-Yuan Yang Li Zhang Wei-Jin Huang Wei Hou Chang-Fa Fan Rong-Hua Jin Ying-Mei Feng You-Chun Wang Jin-Kui Yang Department of Endocrinology Beijing Tongren HospitalCapital Medical UniversityBeijingChina division of hiv/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)BeijingChina Department of Science and Technology Beijing Youan HospitalCapital Medical UniversityBeijingChina division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug ControlBeijingChina

To discover new drugs to combat COVID-19,an understanding of the molecular basis of SARS-CoV-2 infection is urgently ***,for the first time,we report the crucial role of cathepsin L(CTSL)in patients with *** circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and ***,SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo,while CTSL overexpression,in turn,enhanced pseudovirus infection in human *** functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry,as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in ***,amantadine,a licensed anti-influenza drug,significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in ***,CTSL is a promising target for new anti-COVID-19 drug development.

关键词： infection drugs ACE2

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Screening and identification of HTNV_(pv)entry inhibitors with high-throughput pseudovirus-based chemiluminescence

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Virologica Sinica 2022年第4期37卷 531-537页

作者： Xiaojing Wen Li Zhang Qiang Liu Xinyue Xiao Weijin Huang Youchun Wang division of hiv/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)and WHO Collaborating Center for Standardization and Evaluation of BiologicalsBeijing 102629China Department of Microbiological Laboratory Technology School of Public HealthShandong UniversityJinan 250012China Institute for Reference Standards and Standardization National Institutes for Food and Drug ControlBeijing 102629China

Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic *** has the highest incidence of HFRS,which is mainly caused by HTNV and Seoul *** approved antiviral drugs are available for these hantaviral ***,a chemiluminescence-based highthroughput-screening(HTS)assay was developed and used to screen HTNV pseudovirus(HTNVpv)inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine *** identified six compounds with in vitro anti-HTNVpvactivities in the low-micromolar range(EC50values of0.1–2.2μmol/L;selectivity index of 40–900).Among the six selected compounds,cepharanthine not only showed good anti-HTNVpvactivity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 h after infection by94%(180 mg/kg/d,P<0.01),93%(90 mg/kg/d,P<0.01),or 92%(45 mg/kg/d,P<0.01),respectively,in a bioluminescent imaging mouse model.A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry ***,we have established a HTS method for antiviral drugs screening,and shown that cepharanthine is a candidate for HCPS and HFRS *** findings may offer a starting point for the treatment of patients infected with hantaviruses.

关键词： Hantaan virus(HTNV) High-throughput screening(HTS) Inhibitor Drug repurposing

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Comparison of hiv Testing among Children and Adults with Tuberculosis, Vietnam

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Journal of Tuberculosis Research 2017年第4期5卷 292-297页

作者： Tyson Volkmann Binh Nguyen Ebelechukwu G. Anyalechi Kimberly N. Chapman Hedges Ho Van Anh Pham Quang Tue Nguyen Viet Nhung Eleanor S. Click division of Global hiv and TB Centers for Disease Control and Prevention Atlanta USA division of Tuberculosis Elimination Centers for Disease Control and Prevention Atlanta USA Vietnam National Tuberculosis Program Hanoi Vietnam

hiv testing among persons with tuberculosis (TB) results in high-yield identification of persons infected with hiv. To evaluate differences in hiv testing among children versus adults with TB in Vietnam, we collected and analyzed age-disaggregated facility and aggregated provincial data from the National Tuberculosis Program. hiv testing was incompletely documented for >70% of children, whereas adult testing data were >90% complete. Standardized training of personnel for universal hiv testing and documentation for children with TB could improve hiv case-detection and permit linking of children with hiv to antiretroviral treatment to prevent morbidity and mortality.

关键词： Surveillance Operational Research Childhood TB Pediatric

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Uptake of hiv Self-testing among Men Who have Sex with Men in Beijing, China： a Cross-sectional Study

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Biomedical and Environmental Sciences 2017年第6期30卷 407-417页

作者： REN Xian Long WU Zun You MI Guo Dong MCGOOGAN Jennifer ROU Ke Ming ZHAO Yan division of Prevention Intervention National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China Office of the Director National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China division of Treatment and Care National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China

Objective To examine hiv self-testing uptake and its determinates among men who have sex with men （MSM） in Beijing, China. Methods A cross-sectional online survey was conducted in Beijing, China in 2016. Participants were users of a popular Chinese gay networking application and had an unknown or negative hiv status. Univariate and multivariate logistic regression analyses were conducted to examine factors associated with hiv self-testing based on adjusted odds ratio （AOR） and 95% confidence interval （CI）. Results Among the 5,996 MSM included in the study, 2,383 （39.7%） reported to have used hiv self-testing kits. Willingness to use an hiv self-test kit in the future was expressed by 92% of the participants. High monthly income （AOR = 1.49; CI = 1.10-2.02; P = 0.010）, large number of male sex partners （≥2： AOR = 1.24; CI = 2.09-1.43; P = 0.002）, sexual activity with commercial male sex partners （〉 2： AOR = 1.94; CI = 1.34 -2.82; P = 0.001）, long-term drug use （AOR = 1.42; CI = 1.23-1.62; P 〈 0.001）, and long-term hiv voluntary counseling and testing （VCT） attendance （AOR = 3.62; CI = 3.11-4.22; P 〈 0.001） were all associated with increased odds of hiv self-testing uptake. Conclusion The nearly 40% rate of hiv self-testing uptake among MSM in our sample was high. In addition, an over 90% willingness to use kits in the future was encouraging. hiv self-testing could be an important solution to help China achieve the global target of having 90% of all people living with hiv diagnosed by 2020.

关键词： Men who have sex with men hiv self-testing Associated factors Beijing

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Retinal nerve fiber layer changes based on historic CD4 nadir among hiv positive patients undergoing glaucoma evaluation

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International Journal of Ophthalmology(English edition) 2019年第5期12卷 789-794页

作者： Sarah H.Van Tassel Paul Petrakos Elizabeth Marlow Elizabeth Mauer Harjot K.Singh Anna M.Demetriades Department of Ophthalmology Weill Cornell Medicine division of Biostatistics and Epidemiology Department of Healthcare Policy & ResearchWeill Cornell Medicine division of Infectious disease New York-Presbyterian Hospital/Weill Cornell Medicine

AIM: To determine relationships between retinal nerve fiber layer(RNFL) thickness and nadir CD4 cell count in human immunodeficiency virus(hiv) positive patients evaluated for glaucoma ***: Data were reviewed for 329 hiv positive patients evaluated for glaucoma suspicion. High-definition optical coherence tomography(OCT) RNFL measurements were obtained at least 6 mo apart. Analyses were performed to identify relationships between nadir CD4 count and RNFL ***: Totally 110 eyes of 55 patients met inclusion criteria, of which 46 eyes were from subjects with nadir CD4hiv positive patients may be affected by historic hiv disease control and should be considered when evaluating hiv positive patients for glaucoma.

关键词： glaucoma glaucoma suspect human immunodeficiency virus retinal nerve fiber layer

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Epigenomic landscapes during prefrontal cortex development and aging in rhesus

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National Science Review 2024年第8期11卷 75-97页

作者： Chao Ning Xi Wu Xudong Zhao Zongyang Lu Xuelong Yao Tao Zhou Lizhi Yi Yaoyu Sun Shuaishuai Wu Zhenbo Liu Xingxu Huang Lei Gao Jiang Liu National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of Biophysics Chinese Academy of Sciences College of Life Sciences University of Chinese Academy of Sciences division of hiv/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC) State Key Laboratory of Drug Regulatory Science Key Laboratory of Animal Models and Human disease Mechanisms of Chinese Academy of Sciences Kunming Institute of ZoologyChinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Guangzhou Nvwa Life Technology Co. Ltd Shenzhen Neher Neural Plasticity Laboratory CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Key Laboratory of Epigenetic Regulation and Intervention Institute of Biophysics Chinese Academy of Sciences Zhejiang Provincial Key Laboratory of Pancreatic disease The First Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of Medicine Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The prefrontal cortex(PFC) is essential for higher-level cognitive *** epigenetic dynamics participates in PFC development and aging is ***,we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging *** dynamics of chromatin states,including higher-order chromatin structure,chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription,participating in distinct processes of *** changes of epigenetic signals occur around the birth ***,genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent *** identified a cis-regulatory module and the transcription factors(TFs) associated with basal radial glia development,which was associated with large brain size in *** TFs include GLI3,CREB5 and ***,the genes associated with the basal radial glia(bRG)-associated cis-element module,such as SRY and SOX9,are enriched in sex ***-associated single nucleotide polymorphisms are more enriched in super enhancers(SEs) than typical enhancers,suggesting that SEs play an important role in neural network wiring.A cis-regulatory element of DBN1 is identified,which is critical for neuronal cell proliferation and synaptic neuron ***,the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging,which are associated with abnormal expression of aging-related genes and transposon activation,***,our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

关键词： rhesus macaque prefrontal cortex 3D genomics chromatin immunoprecipitation sequencing development aging

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Morbidity Analysis of the Notifiable Infectious diseases in China,2018

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China CDC weekly 2019年第4期1卷 47-53页

作者： Shuaibing Dong Xiang Ren Cuihong Zhang Mengjie Geng Yuliang Zhu Lusha Shi Lijie Zhang Zhongjie Li Liping Wang division of Infectious disease Key Laboratory of Surveillance and Early Warning on Infectious DiseaseChina CDCBeijingChina Fuyang CDC AnhuiChina Heilongjiang CDC HeilongjiangChina Complex Systems Research Center Shanxi UniversityShanxiChina

Introduction Notifiable infectious disease surveillance is important for understanding the trends in morbidity for certain diseases,especially detection of acute infectious disease outbreaks and changing epidemiology.A web-based reporting system was deployed in January 2004,which has improved data collection and speed *** report provides an updated analysis for reports published in 2013 and *** Data from the National Notifiable disease Reporting System(NNDRS)was *** NNRDS shows data from 39 notifiable diseases split into three categories(A,B,and C)based on severity and importance.A descriptive analysis was conducted to analyze the morbidity of notifiable diseases in *** In 2018,the morbidity of national notifiable diseases was 559.41 per 100,000 population,an increase of 12.88% compared with the average of 2015–*** proportion of laboratory confirmed cases was 36.22%,which decreased 4.03% compared with the average of that in the recent three *** transmitted by direct contact/fecal–oral transmission accounted for the largest proportion,49.37% of the total reported cases,followed by the respiratory transmitted diseases,blood-borne/sexually transmitted diseases,and the zoonotic and vectorborne diseases with a proportion of 25.18%,24.60%,and 0.85%,*** descriptive analysis showed that the viral-infected cases accounted for 73.78% of the totals,followed by the bacterialinfected and parasitic *** The national morbidity of notifiable infectious diseases showed increases in 2018,mostly due to higher morbidity of category C diseases,such as HFMD,infectious diarrhea,and influenza,and these diseases need to be further prioritized in disease control and prevention *** confirmed cases remain low and need to be improved to improve data quality.

关键词： diseases epidemiology prevention

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Clinical Features and Corrected Factors with Neurosyphilis in hiv/Syphilis Co-Infected Patients Based on Stage of Syphilis

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International Journal of Dermatology and Venereology 2022年第2期5卷 61-67页

作者： Yuan-Yuan Wang Mei Shi Zhi-Fang Guan Lei Zhang Xin Gu Hai-Kong Lu Teng-Fei Qi Li-Yan Ni Juan Wu Wei Zhao Rui-Rui Peng Lin Zhu Ping-Yu Zhou sexually transmitted disease Institute Shanghai Skin Disease HospitalClinical School of Anhui Medical UniversityShanghai 200050China sexually transmitted disease Institute Shanghai Skin Disease HospitalTongji UniversitySchool of MedicineShanghai 200050China China-Australia Joint Research Center for Infectious diseases School of Public HealthXi’an Jiaotong University Health Science CentreXi’anShaanxi 710049China Melbourne Sexual Health Centre Alfred HealthMelbourne 3800Australia Central Clinical School Faculty of MedicineNursing and Health SciencesMonash UniversityMelbourne 3800Australia Department of Epidemiology and Biostatistics College of Public HealthZhengzhou UniversityZhengzhouHenan 450001China.

Objective: Neurosyphilis is challenging to diagnose, especially in patients with human immunodeficiency virus (hiv)/syphilis co-infection. The aim of this study was to profile the clinical features of neurosyphilis and evaluate the correlation between neurosyphilis and clinical or laboratory factors among patients with hiv/syphilis ***: We retrospectively analyzed the data of 479 hiv/syphilis co-infected patients examined between August 2009 and September 2018. A multivariate logistic regression model was used to identify factors correlated with ***: The overall prevalence of neurosyphilis was 21.7%. The prevalence of neurosyphilis differed among patients with primary (11.1%), secondary (20.1%), and latent syphilis (29.1%). The prevalences of neurosyphilis in patients with serological non-response and serofast patients were 26.1% and 6.3%, respectively, while 12.5% of patients with serological relapse had neurosyphilis. Patients with secondary and latent syphilis had serum rapid plasma reagin (RPR) titers (per unit) of 1.44-fold [95% confidence interval (CI): 1.08-1.93,P= 0.014] and 2.73-fold (95%CI: 1.49-5.00,P= 0.001), respectively, which increased the risk of confirmed neurosyphilis. Among patients with latent syphilis, a serum RPR titer of ≥1:32 and peripheral blood CD4 cell count of ≤350/mL were significantly associated with neurosyphilis, with adjusted odds ratios of 9.45 (95%CI: 1.86-48.03,P= 0.007) and 3.75 (95%CI: 1.11-12.66,P= 0.033), ***: A serum RPR titer of ≥1:32 and a peripheral blood CD4 cell count of ≤350/mL have predictive value in screening for neurosyphilis among hiv-positive patients with latent syphilis.

关键词： human immunodeficiency virus syphilis neurosyphilis correlated factors

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