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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 ***,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

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Type Ⅰ interferon receptor knockout mice as models for infection of highly pathogenic viruses with outbreak potential

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Zoological Research 2018年第1期39卷 3-14页

作者： gary wong Xiang-Guo Qiu Shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious DiseaseShenzhen Third People's HospitalShenzhen Guangzhou 518020China Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Special Pathogens Program National Microbiology LaboratoryPublic Health Agency of CanadaWinnipegManitoba R3E 3R2Canada Department of Medical Microbiology and Infectious Diseases University of ManitobaWinnipegManitoba R3E 0J9Canada

Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.

关键词： Ifnar Mice Animal model Flavivirus Filovirus Arenavirus Bunyavirus Henipavirus Togavirus

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Did ZIKV evolve to be more dangerous? A new clue towards neurovirulence

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National Science Review 2018年第2期5卷 121-122页

作者： gary wong George F.Gao Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases Shenzhen Key Laboratory of Pathogen and Immunity Shenzhen Third People's Hospital CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences

Before 2015,Zika virus(ZIKV)was a little-known flavivirus that caused sporadic symptomatic infections in humans(under 20 reported cases,but likely manymore unreported asymptomatic cases)in the decades following its di... 详细信息

关键词： ZIKA virus FLAVIVIRUSES EPIDEMICS

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Animal models for filovirus infections

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Zoological Research 2018年第1期39卷 15-24页

作者： Vinayakumar Siragam gary wong Xiang-Guo Qiu Special Pathogens Program Public Health Agency of CanadaWinnipegManitoba R3E 3R2Canada Department of Medical Microbiology University of ManitobaWinnipegManitoba R3E 0J9Canada Shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious DiseaseShenzhen Third People's HospitalShenzhen Guangzhou 51 8020China Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates （NHPs）, causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.

关键词： Filovirus Ebola virus Marburg virus Marburg virus disease Ebola virus disease Mouse-adapted ebolavirus Guinea-pig-adapted ebolavirus Sudan virus Plaque-forming units

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Advances in treatment strategies for COVID-19:Insights from other coronavirus diseases and prospects

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Biosafety and Health 2023年第5期5卷 272-279页

作者： Yingwen Li Jiaming Lan gary wong Viral Hemorrhagic Fevers Research Unit C.A.S.Key Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China

The coronavirus disease 2019(COVID‐19)pandemic is the third human disease outbreak caused by an emerging coronavirus in the 21st *** by severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),the COVID‐19 pandemic has been the most devastating,with millions of *** countermeasures are needed to limit the number of infections and ***,we discuss advances in clinical and research‐based treatment methods for SARS‐CoV‐2 that were initially derived from treatments for other *** advances in SARS‐CoV‐2 treatments,from traditional drugs and immunotherapies to artificial intelligence to predict potential future treatment methods,are summarized and discussed.

关键词： SARS‐CoV‐2 COVID‐19 Treatment Strategies Potential treatments

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Can Ebola virus become endemic in the human population？

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Protein & Cell 2016年第1期7卷 4-6页

作者： gary wong George F. Gao Xiangguo Qiu Special Pathogens Program National Microbiology Laboratory Public Health Agency of Canada Winnipeg MB CanadaDepartment of Medical Microbiology University of Manitoba Winnipeg MB Canada Department of Medical Microbiology University of Manitoba Winnipeg MB Canada CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of SciencesBeijing 100101 China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 100052 China Officeof Director-General Chinese Center for Disease Control and Prevention Beijing 102206 China

The 2014-15 Ebola virus reported during March 2014 Guinea. has shown itself to （EBOV） outbreak, originally n the Western African nation of be resistant to traditional con- tainment methods, with over 28,000 infections and 11,000 deaths over 18 months. Recently, news that a Scottish nurse had relapsed to EBOV disease with neurological symptoms at 10 months after recovery have astonished experts. The prolonged nature of the outbreak has led to questions whether EBOV can become endemic in the human popula- tion, an undesirable outcome due to the large amount of resources required to keep this virus under control. In this commentary, we discuss aspects EBOV disease with those caused by pathogens considered endemic in humans, as well as factors which may contribute to sustained EBOV transmission in humans.

关键词： High Case Fatality Rate EBOV Infection Severe Hemorrhagic Fever Minor Public Health EBOV Outbreak

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Bat origin of a new human coronavirus:there and back again

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Science China(Life Sciences) 2020年第3期63卷 461-462页

作者： Xiang Li Yuhe Song gary wong Jie Cui CAS Key Laboratory of Molecular Virology&Immunology Institut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China Center for Biosafety Mega-Science Chinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China School of Life Sciences Shanghai UniversityShanghai 200444China

A novel coronavirus reported to cause pneumonia in 41 people during December 2019 in Wuhan,the capital of Hubei province,China,was identified and designated as the 2019 novel coronavirus(2019-nCoV)(Zhu et al.,2020;Li et al.,2020).Infection with 2019-nCoV results in clusters of severe respiratory illness similar to that caused by severe acute respiratory syndrome coronavirus(SARS-CoV)and is associated with high mortality(Chen et al.,2020;Huang et al.,2020).This new coronavirus belongs to genus Betacoronavirus,family Coronaviridae,with a single-stranded,positive-sense RNA genome,but genetically distinct from SARS-CoV and Middle East respiratory syndrome coronavirus(MERS-CoV).

关键词： Middle origin belongs

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Zika virus in the testes： should we be worried？

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Protein & Cell 2017年第3期8卷 162-164页

作者： gary wong Shihua Li Lei Liu Yingxia Liu Yuhai Bi Shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious Disease Shenzhen Third People's_ Hospital Shenzhen 518112 China CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Center for Influenza Research and Early-warning (CASCIRE) Chinese Academy of Sciences Beijing 100101 China

Zika virus （ZIKV） is a mosquito-borne pathogen from the family Flaviviridae, and infection of humans with ZIKV through mosquito bites may result in a disease known as Zika fever. Most Zika fever cases are asymptomatic and thus go unreported, but if symptoms do appear, they are usually mild in nature （fever, joint pain, headache and macu- Iopapular rash）, and self-resolve within one week （Chen and Hamer 2016）. No deaths have ever been attributed to Zika fever; however, when a woman is infected with ZIKV during pregnancy, vertical transmission of the virus may result in microcephaly in the offspring （Rasmussen, Jamieson et al., 2016）. ZIKV infections in adults are associated with episodes of Guillain-Barr6 syndrome, an autoimmune disorder of the peripheral nervous system, resulting in rapid-onset muscle weakness （Cao-Lormeau, Blake et al. 2016）.

关键词： Nonhuman Primate Dengue Virus Male Reproductive System Cynomolgus Macaque Vaginal Fluid

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Application of animal models to compare and contrast the virulence of current and future potential SARS-CoV-2 variants

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Biosafety and Health 2022年第3期4卷 154-160页

作者： Zhe Ding Tong Chen Jiaming Lan gary wong Viral Hemorrhagic Fevers Research Unit CAS Key Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100190China

Since severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)was first identified during late 2019,the sustained spread of this pathogen within the human population has caused worldwide disruption with staggering infection rates and death *** to the accumulation of mutations in SARS‐CoV‐2,the virus has evolved into many variants,five of which have been listed as variants of concern VOCs by the World Health Organization(WHO).Multiple animal models of SARS‐CoV‐2 have been developed to evaluate vaccines and drugs and to assess the pathogenicity,transmissibility and antiviral measures of these ***,we review the cutting‐edge research based on mouse,hamster,ferret and non‐human primate models for evaluating SARS‐CoV‐2 with a focus on the Omicron variant,and highlight the importance of updating vaccines in a timely manner in order to mitigate the negative effects of SARS‐CoV‐2 infections in the human population.

关键词： SARS‐CoV‐2 Animal models Variants of concern Omicron

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Zoonotic origins of human coronavirus 2019(HCoV-19/SARS-CoV-2):why is this work important?

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Zoological Research 2020年第3期41卷 213-219页

作者： gary wong Yu-Hai Bi Qi-Hui Wang Xin-Wen Chen Zhi-Gang Zhang Yong-Gang Yao CAS Key Laboratory of Molecular Virology&Immunology Institut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China Department of Microbiology-Infectiology and Immunology Laval UniversityQuebec G1V 4G2Canada CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyCenter for Influenza Research and Early-warning(CASCIRE)CAS-TWAS Center of Excellence for Emerging Infectious Diseases(CEEID)Chinese Academy of SciencesBeijing 100101China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhanHubei 430071China State key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan School of Life SciencesYunnan UniversityKunmingYunnan 650091China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.

关键词： origin why is this work important HCoV-19/SARS-CoV-2 Zoonotic origins of human coronavirus 2019

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