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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 worldwide.Unfortunately,state-of-the-art treatments still lag behind the continual emergence of new variants.Key to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural evolution.Here,we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne(EDY)molecules.The 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 molecules.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

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Monkeypox virus:a re-emergent threat to humans

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Virologica Sinica 2022年第4期37卷 477-482页

作者： Qizan Gong Changle Wang Xia Chuai sandra chiu Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei230026China Department of Pathogenic Biology Hebei Medical UniversityShijiazhuangHebei050017China

Human monkeypox(MPX)is a rare zoonotic infection characterized by smallpox-like signs and symptoms.It is caused by monkeypox virus(MPXV),a double stranded DNA virus belonging to the genus Orthopoxvirus.MPX was first identified in 1970 and mostly prevailed in the rural rainforests of Central and West Africa in the past.Outside Africa,MPX was reported in the United Kingdom,the USA,Israel,and Singapore.In 2022,the resurgence of MPX in Europe and elsewhere posed a potential threat to humans.MPXV was transmitted by the animals-human or human-human pathway,and the symptoms of MPXV infection are similar to that of smallpox,but in a milder form and with lower mortality(1%–10%).Although the smallpox vaccination has been shown to provide 85%protection against MPXV infection,and two anti-smallpox virus drugs have been approved to treat MPXV,there are still no specific vaccines and drugs against MPXV infection.Therefore it is urgent to take active measures including the adoption of novel anti-MPXV strategies to control the spread of MPXV and prevent MPX epidemic.In this review,we summarize the biological features,epidemiology,pathogenicity,laboratory diagnosis,and prevention and treatment strategies on MPXV.This review provides the basic knowledge for prevention and control of future outbreaks of this emerging infection.

关键词： Monkeypox virus(MPXV) Orthopoxvirus Smallpox vaccine Antiviral drugs

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HBV precore G1896A mutation promotes growth of hepatocellular carcinoma cells by activating ERK/MAPK pathway

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Virologica Sinica 2023年第5期38卷 680-689页

作者： Baoxin Zhao Hongxiu Qiao Yan Zhao Zhiyun Gao Weijie Wang Yan Cui Jian Li Zhanjun Guo Xia Chuai sandra chiu Institute of Medical and Health Science Hebei Medical UniversityShijiazhuang050017China Department of Pathogen Biology Hebei Medical UniversityShijiazhuang050017China Department of Gastroenterology and Hepatology The Fourth Hospital of Hebei Medical UniversityShijiazhuang050000China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega ScienceChinese Academy of SciencesWuhan430207China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei230026China

Chronic hepatitis B virus(HBV)infection is one of the leading causes of hepatocellular carcinoma(HCC).The HBV genome is prone to mutate and several variants are closely related to the malignant transformation of liver disease.G1896A mutation(G to A mutation at nucleotide 1896)is one of the most frequently observed mutations in the precore region of HBV,which prevents HBeAg expression and is strongly associated with HCC.However,the mechanisms by which this mutation causes HCC are unclear.Here,we explored the function and molecular mechanisms of the G1896A mutation during HBV-associated HCC.G1896A mutation remarkably enhanced the HBV replication in vitro.Moreover,it increased tumor formation and inhibited apoptosis of hepatoma cells,and decreased the sensitivity of HCC to sorafenib.Mechanistically,the G1896A mutation could activate ERK/MAPK pathway to enhanced sorafenib resistance in HCC cells and augmented cell survival and growth.Collectively,our study demonstrates for the first time that the G1896A mutation has a dual regulatory role in exacerbating HCC severity and sheds some light on the treatment of G1896A mutation-associated HCC patients.

关键词： HBV G1896A mutation Hepatocellular carcinoma(HCC) Proliferation Apoptosis ERK/MAPK

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Ebola virus VP35 perturbs type I interferon signaling to facilitate viral replication

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Virologica Sinica 2023年第6期38卷 922-930页

作者： Zengguo Cao Chenchen Liu Cheng Peng Yong Ran Yulin Yao Gengfu Xiao Entao Li Zixi Chen Xia Chuai sandra chiu Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100190China National Biosafety Laboratory Chinese Academy of SciencesWuhan430020China Division of Life Sciences and Medicine University of Science and Technology of Chin1Hefei230026China Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science Shenzhen Engineering Laboratory for Marine Algal BiotechnologyGuangdong Provincial Key Laboratory for Plant EpigeneticsCollege of Life Sciences and OceanographyShenzhen UniversityShenzhen 518060China

As one of the deadliest viruses,Ebola virus(EBOV)causes lethal hemorrhagic fevers in humans and nonhuman primates.The suppression of innate immunity leads to robust systemic virus replication of EBOV,leading to enhanced transmission.However,the mechanism of EBOV-host interaction is not fully understood.Here,we identified multiple dysregulated genes in early stage of EBOV infection through transcriptomic analysis,which are highly clustered to Jak-STAT signaling.EBOV VP35 and VP30 were found to inhibit type I interferon(IFN)signaling.Moreover,exogenous expression of VP35 blocks the phosphorylation of endogenous STAT1,and suppresses nuclear translocation of STAT1.Using serial truncated mutations of VP35,N-terminal 1–220amino acid residues of VP35 were identified to be essential for blocking on type I IFN signaling.Remarkably,VP35 of EBOV suppresses type I IFN signaling more efficiently than those of Bundibugyo virus(BDBV)and Marburg virus(MARV),resulting in stable replication to facilitate the pathogenesis.Altogether,this study enriches understanding on EBOV evasion of innate immune response,and provides insights into the interplay between filoviruses and host.

关键词： Ebola virus(EBOV) Type I interferon(IFN)signaling Viral replication

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A visual assay panel for the identification of monkeypox virus DNA belonging to the clades I and II

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Virologica Sinica 2023年第4期38卷 635-638页

作者： Pei Huang Zanheng Huang Meihui Liu Yujie Bai Hongli Jin Jingbo Huang Xingqi Liu Zhenhong Guan Ming Duan Haili Zhang Yuanyuan Li sandra chiu Hualei Wang State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Key Laboratory for Zoonosis Research of the Ministry of EducationInstitute of ZoonosisCollege of Veterinary MedicineJilin UniversityChangchun130062China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei244199China

Dear Editor,Monkeypox virus(MPXV)is an enveloped double-stranded DNA virus belonging to the family Poxviridae,subfamily Chordopoxvirinae,and genus Orthopoxvirus(Hraib et al.,2022;Gong et al.,2022).MPXV forms Congo Basin clade(clade I)and West African clade(clade II)(Durski et al.,2018).Additionally,clade II consists of two subclades,clade IIa and clade IIb.

关键词： belong panel African

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A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3584-3591页

作者： Xinghai Zhang Huajun Zhang Tingting Li Shaohong Chen Feiyang Luo Junhui Zhou Peiyi Zheng Shuyi Song Yan Wu Tengchuan Jin Ni Tang Aishun Jin Chengyong Yang Guofeng Cheng Rui Gong sandra chiu Ailong Huang CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430o71 HubeiChina Department of Immunology College of Basic MedicineChongqing Medical UniversityChongqing 400010China Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology Chongqing Medical UniversityChongqing 400010China University of Chinese Academy of Sciences 100049 BeijingChina Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230026 AnhuiChina Key Laboratory of Molecular Biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing 400010China Mindao Haoyue Co LtdSQ0042 Lanyuan HallNo.61 Daxuecheng Middle RoadChongqing 400042China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.

关键词： nasal dosage prevention

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Duration of humoral immunity from smallpox vaccination and its cross-reaction with Mpox virus

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4942-4948页

作者： Entao Li Xiaoping Guo Dongxiang Hong Qizan Gong Wenyu Xie Tingting Li Jian Wang Xia Chuai sandra chiu Department of Laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhuiChina Department of Clinical Laboratory First Affiliated Hospital of Anhui Medical UniversityHefeiAnhuiChina State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega ScienceChinese Academy of SciencesWuhanHubeiChina Core Unit of National Clinical Research Center for Laboratory Medicine HefeiAnhuiChina Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases HefeiAnhuiChina

The ongoing pandemic caused by mpox virus(MPxV)has become an international public health emergency that poses a significant threat to global health.The vaccinia virus Tiantan strain(VTT)was used to vaccinate against smallpox in China 42 years ago.It is urgent to assess the level of immunity to smallpox in individuals vaccinated 43 or more years ago and evaluate their immunological susceptibility to MPxV.

关键词： immunity vaccination susceptibility

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Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques

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Protein & Cell 2023年第1期14卷 69-73页

作者： Dali Tong Mei Zhang Yunru Yang Han Xia Haiyang Tong Huajun Zhang Weihong Zeng Muziying Liu Yan Wu Huan Ma Xue Hu Weiyong Liu Yuan Cai Yanfeng Yao Yichuan Yao Kunpeng Liu Shifang Shan Yajuan Li Ge Gao Weiwei Guo Yun Peng Shaohong Chen Juhong Rao Jiaxuan Zhao Juan Min Qingjun Zhu Yanmin Zheng Lianxin Liu Chao Shan Kai Zhong Zilong Qiu Tengchuan Jin sandra chiu Zhiming Yuan Tian Xue First Affiliated Hospital of USTC School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Hefei National Research Center for Physical Sciences at the Microscale Neurodegenerative Disorder Research CenterCAS Key Laboratory of Brain Function and DiseaseCAS Key Laboratory of Innate Immunity and Chronic DiseaseBiomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230026China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Center for Biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Hefei Institutes of Physical Science Chinese Academy of SciencesHefei 230031China Anhui Institute of Pediatric Research Anhui Provincial Children's HospitalHefei 230051China Chinese Academy of Sciences Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Department of Clinical Laboratory First Affiliated Hospital of Anhui Medical UniversityHefei230022China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Dear Editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health emergency.The disease shows a high infection rate,long incubation period,and rapidly emerging variants,which have led to its rapid spread worldwide(Krammer 2020).Many vaccines have been developed for the control of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for COVID-19,including vaccines based on messenger RNA(mRNA)(Polack et al.2020),viral vectors(Zhu et al.2020),recombinant proteins(Yang et al.2020),and inactivated SARS-CoV-2(Zhang et al.2021).

关键词： respiratory acute

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物理疗法在脑科疾病中的前沿应用:神经治疗学的复兴

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科学通报 2018年第25期63卷 2592-2598页

作者：路翰娜陈秀雯林翠华郑柏荣陈伟智何红波赵素华宁玉萍广州医科大学附属脑科医院广州510370 香港中文大学医学院精神科学系神经调节实验室香港999077 香港中文大学医学院陈慧慧基金身心认知运动中心香港999077 香港大学医学院精神科学系香港999077

神经系统疾病在全球疾病负担和致残率的排位中居高不下,但对其致病机理与个体化治疗方案的研究却较为局限.从生物能量学的视角,神经精神疾病涉及脑能量/代谢(例如熵)的异常.在物理学中的电、磁、光、波为4种常见的能量形式,而基于这4种... 详细信息

神经系统疾病在全球疾病负担和致残率的排位中居高不下,但对其致病机理与个体化治疗方案的研究却较为局限.从生物能量学的视角,神经精神疾病涉及脑能量/代谢(例如熵)的异常.在物理学中的电、磁、光、波为4种常见的能量形式,而基于这4种能量形式的神经调控技术不仅在脑科学研究中占有重要一席,同时也在脑科疾病的治疗中逐渐成为非药物治疗的重要方法.本综述旨在介绍基于电、磁、光、波4种能量存在方式的神经调控方法在脑科疾病的前沿研究、技术难题与未来应用前景.

关键词：神经调控经颅电刺激经颅磁刺激深部脑刺激个体差异神经可塑性复原力

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