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Stress proteins:the biological functions in virus infection,present and challenges for target-based antiviral drug development

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1363-1402页

作者： Qianya Wan Dan Song Huangcan Li ming-liang he Department of Biomedical Sciences City University of Hong KongKowloonHong KongChina CityU Shenzhen Research Institute ShenzhenChina

Stress proteins(SPs)including heat-shock proteins(HSPs),RNA chaperones,and ER associated stress proteins are molecular chaperones essential for cellular *** major functions of HSPs include chaperoning misfolded or unfolded polypeptides,protecting cells from toxic stress,and presenting immune and inflammatory *** as a double-edged sword,HSPs also cooperate with numerous viruses and cancer cells to promote their *** chaperones are a group of heterogeneous nuclear ribonucleoproteins(hnRNPs),which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase *** involve in a large number of cellular processes,including chromatin remodelling,transcription regulation,RNP assembly and stabilization,RNA export,virus replication,histonelike nucleoid structuring,and even intracellular *** of stress proteins is associated with many human diseases including human cancer,cardiovascular diseases,neurodegenerative diseases(e.g.,Parkinson’s diseases,Alzheimer disease),stroke and infectious *** this review,we summarized the biologic function of stress proteins,and current progress on their mechanisms related to virus reproduction and diseases caused by virus *** SPs also attract a great interest as potential antiviral targets(e.g.,COVID-19),we also discuss the present progress and challenges in this area of HSP-based drug development,as well as with compounds already under clinical evaluation.

关键词： metabolism stabilization summarized

Pandemic COVID-19:Current status and challenges of antiviral therapies

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Genes & Diseases 2020年第4期7卷 502-519页

作者： Winglam Chan Betsy he Xiong Wang ming-liang he Department of Biomedical Sciences City University of Hong KongHong KongChina Rensselaer Polytechnic Institute TroyNYUSA CityU Shenzhen Research Institute NanshanShenzhenChina

The pandemic COVID-19,caused by a new coronavirus SARS-CoV-2 infection,has infected over 12 million individuals and caused more than 55,200 death ***,there is no specific drug to treating this *** we summarized the mechanisms of antiviral therapies and the clinic findings from different *** chemotherapies have been conducted by in multiple cohorts in different *** FDA has fast approved remdesivir for treating COVID-19,it only speeds up recovery from COVID-19 with mildly reduced *** chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects,it is imperative high-quality data from worldwide clinical trials are necessitated for an approved *** terms of hydroxychloroquine(HCQ)therapy,although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients,large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the *** plasma(CP)therapy suggested its safety use in SARS-CoV-2 infection;but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human *** research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis,suitable animal models or ex vivo human lung tissues aid in studying replication,transmission and spread of the novel viruses,thereby facilitating highly effective therapies.

关键词： Chloroquine Convalescent plasma therapy COVID-19 Hydroxychloroquine Ivermectin Natural killer cell therapy Remdesivir SARS-CoV-2

RNA interference and antiviral therapy

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World Journal of Gastroenterology 2007年第39期13卷 5169-5179页

作者： Yan Na Chu-Yan Chan ming-liang he Stanley Ho Centre for Emerging Infectious Diseases and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Hong Kong China

RNA interference (RNAi) is an evolutionally conserved gene silencing mechanism present in a variety of eukaryotic species. RNAi uses short double-stranded RNA (dsRNA) to trigger degradation or translation repression of homologous RNA targets in a sequence-specific manner. This system can be induced effectively in vitro and in vivo by direct application of small interfering RNAs (siRNAs), or by expression of short hairpin RNA (shRNA) with non-viral and viral vectors. To date, RNAi has been extensively used as a novel and effective tool for functional genomic studies, and has displayed great potential in treating human diseases, including human genetic and acquired disorders such as cancer and viral infections. In the present review, we focus on the recent development in the use of RNAi in the prevention and treatment of viral infections. The mechanisms, strategies, hurdles and prospects of employing RNAi in the pharmaceutical industry are also discussed.

关键词： RNA interference Short hairpin RNA Micro RNA Antiviral therapy Viral infection Humanimmunodeficiency virus hepatitis C virus hepatitis Bvirus SARS-coronavirus

Viral kinetics of Enterovirus 71 in human habdomyosarcoma cells

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World Journal of Gastroenterology 2011年第36期17卷 4135-4142页

作者： Jing Lu Li-Na Yi Hsiang-Fu Kung ming-liang he Ya-Qing he Hong Zan Stanley Ho Center for Emerging Infectious Diseases and Li Ka Shing Institute of Health SciencesFaculty of MedicineThe Chinese University of Hong KongHong KongChina Shenzhen Center for the Disease Control and Prevention Shenzhen 518055Guangdong ProvinceChina Institute for Immunology University of California at IrvineCA 92697United States

AIM:To characterise the viral kinetics of enterovirus 71 (EV71).METHODS:In this study,human rhabdomyosarcoma (RD) cells were infected with EV71 at different multiplicity of infection (MOI).After infection,the cytopathic effect (CPE) was monitored and recorded using a phase contrast microscope associated with a CCD camera at different time points post viral infection (0,6,12,24 h post infection).Cell growth and viability were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both EV71 infected and mock infected cells at each time ***71 replication kinet-ics in RD cells was determined by measuring the total intracellular viral RNA with real-time reverse-transcription polymerase chain reaction (qRT-PCR).Also,the intracellular and extracellular virion RNA was isolated and quantified at different time points to analyze the viral package and *** expression of viral protein was determined by analyze the levels of viral structure protein VP1 with Western ***:EV71 infection induced a significant CPE as early as 6 h post infection (p.i.) in both RD cells infected with high ratio of virus (MOI 10) and low ratio of virus (MOI 1).In EV71 infected cells,the cell growth was inhibited and the number of viable cells was rapidly decreased in the later phase of ***71 virions were uncoated immediately after *** intracellular viral RNA began to increase at as early as 3 h *** the exponential increase was found between 3 h to 6 h *** both infected *** viral structure protein synthesis,results from western-blot showed that intracellular viral protein VP1 could not be detected until 6 h *** the cells infected at either MOI 1 or MOI 10;and reached the peak at 9 h *** the cells infected with EV71 at both MOI 1 and MOI ***,the viral package and secretion were also actively processed as the virus underwent rapid *** viral package kinetics was comparable for both MOI 1

关键词： Enterovirus 71 Quantitative reverse transcription polymerase chain reaction Viral kinetics Western blotting

Secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity

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Signal Transduction and Targeted Therapy 2023年第10期8卷 5046-5058页

作者： Huangcan Li Xiong Wang Yiran Wang Yichen Li Ying Chen Yin-Ting Wong Jufang he ming-liang he Department of Biomedical Sciences City University of Hong KongHong KongChina CityU Shenzhen Research Institute NanshanShenzhenChina Department of Neurosciences City University of Hong KongHong KongChina

variety of ways to antagonize host defense through eliminating IFN-signaling intracellularly for ***,the way by viruses target IFN-signaling extracellularly has not been *** by both coronavirus SARS-CoV-2 and enterovi... 详细信息

关键词： immunity diseases eliminating

Saikosaponin D suppresses enterovirus A71 infection by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2019年第1期4卷 602-613页

作者： Chang Li Lihong Huang Wei Sun Ying Chen ming-liang he Jianbo Yue heather Ballard School of Biomedical Sciences University of Hong KongHong KongChina City University of Hong Kong ShenZhen Research Institute ShenZhenChina Department of Biomedical Sciences City University of Hong KongHong KongChina

The dysregulation of autophagy,an evolutionarily conserved lysosomal degradation process,has been implicated in a wide variety of human diseases,and thus,small chemicals that modulate autophagy have therapeutic ***,we assessed the ability of active components isolated from Bupleurum falcatum,a popular Chinese herb,to modulate *** found that saikosaponin D(SsD)and A(SsA)but not C(SsC)potently and reversibly inhibited the fusion of autophagosomes and lysosomes,resulting in the accumulation of autophagosomes,an increased lysosomal pH,and TFEB nuclear ***5A knockdown or the expression of a dominant-negative RAB5 mutant significantly reduced the ability of SsD or SsA to block *** A71(EV-A71),the cause of hand-foot-mouth disease,has been shown to induce *** found that SsD potently inhibited EV-A71 RNA replication and subsequent viral protein synthesis,thereby preventing EV-A71-induced cell ***5 knockdown inhibited EV-A71 viral protein synthesis,whereas autophagy induction by rapamycin promoted *** together,our data indicate that SsD and SsA are potent late-stage autophagy inhibitors that can be used to prevent EV-A71 infection.

关键词： inhibited inhibiting assessed

Attenuating innate immunity and facilitating β-coronavirus infection by NSP1 of SARS-CoV-2 through specific redistributing hnRNP A2/B1 cellular localization

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3174-3176页

作者： Fanghang Zhou Qianya Wan Sheng Chen Ying Chen Pui-Hui Wang Xi Yao ming-liang he Department of Biomedical Sciences City University of Hong KongKowloonHong Kong SARChina Advanced Medical Research Institute Cheeloo College of MedicineShandong University250012JinanShandongChina CityU Shenzhen Research Institute NanshanShenzhenChina

Dear Editor,Evidence shows the NSP1’s crucial roles of theβ-coronavirus SARS-CoV-2 in promoting cellular mRNA degradation,inhibiting host cell translation,innate immunity,and inducing inflammatory cytokine storm in the pathogenesis of COVID-19.1,2 More interestingly,NSP1 deletion in infectious clones prevents virus infection.3 However,little is known how NSP1 interacts with host factors to disrupt the host’s innate immunity for facilitating virus infection and *** a(+)ssRNA virus,SARS-CoV-2 completes its life cycle in the cytosol;viral RNA processing is the key for controlling and regulating the virus reproduction and *** ribonucleoproteins hnRNPs are the main factors responsible for RNA processing,including RNA splicing,maturation,decay,and translation,and even innate immunity in some cases.

关键词： NSP1 immunity infection

A Simple-Prepared and Multi-Reusable Adhesive Based on Epoxy Vitrimer

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Chinese Journal of Polymer Science 2024年第10期42卷 1589-1594,I0015页

作者： Yu-Ting Wang Huan liang Yen Wei Jian-Long Wang Xiang-ming he Yang Yang Institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing100084China The Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology(Ministry of Education) Department of ChemistryTsinghua UniversityBeijing100084China

Adhesives play an important role in modern society's production and daily *** robust and sustainable adhesives remains a great *** we report a sustainable epoxy-vitrimer adhesive with high adhesive strength(about 10 MPa)and reusability(82%strength after 3 times).This adhesive can be fabricated from commercially available products through a straightforward hot-pressing method without the need of *** adhesive process is also simple,requiring only 30 min at 180℃.In addition,the vitrimer adhesive has the advantages of both erasability for reuse and excellent water *** work provides a facile strategy to fabricate high-strength adhesive that ensures reusability,recyclability,low cost of raw materials,and simple processing ***,it expands the range of potential applications for epoxy vitrimers.

关键词： Epoxy Vitrimer Adhesive Reusable Sustainable

Genetic variability of CYP2B6 polymorphisms in four southern Chinese populations

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World Journal of Gastroenterology 2007年第14期13卷 2100-2103页

作者： Bing-Ying Xu Li-Ping Guo Shui-Shan Lee Qing-ming Dong Yi Tan Hong Yao Li-Hua Li Che-Kit Lin Hsiang-Fu Kung ming-liang he Kunming Medical College Kunming 650032 Yunnan Province China Stanley Ho Center for Emerging Infectious Diseases and Li Ka Shing Institute of Health Sciences The Chinese University ofHong Kong Hong Kong China Department of Microbiology Faculty of Medicine The Chinese University of Hong Kong Hong Kong China Hong Kong Red Cross Blood Transfusion Service Hong Kong China

AIM： To investigate the genotype and allelic frequencies of Cytochrome P450 2B6 polymorphisms in four southern Chinese populations.METHODS： DNA was obtained from blood samples from Han Chinese from Hong Kong and three minority groups,the Wa, Bulang and Lahu from Yunnan in southern China. Genotyping was performed using real-time PCR and confirmed by direct sequencing.RESULTS： A total of 507 subjects from southern China were studied. Results showed there is a high prevalence of 516G 〉 T （34.5%） in ethnic Chinese compared to literature reports on other Asian populations and Caucasians. The frequency of the 516TT genotype is higher in the Hah majority （23.1%） than in three other ethnic minority groups （i.e., 7.4%, 9.1% and 15.8%） in southern China.CONCLUSION： This was the first study to document the spectrum of CYP2B6 allelic variants and genotypes in a southern Chinese population. The 516G 〉 T allele is associated with a defective metabolism of efavirenz （EFV）, which therefore may predispose to drug *** regimens for human immunodeficiency virus （HIV） and heroin addiction may need to be optimized in different populations because of the marked variability of the key metabolizing enzyme.

关键词： Polymorphism Allele Genotype Ethnicity Discrimination PCR