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Nanobodies with cross-neutralizing activity provide prominent therapeutic efficacy in mild and severe COVID-19 rodent models

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Virologica Sinica 2023年第5期38卷 787-800页

作者： Qiuxue Han Shen Wang Zhenshan Wang Cheng Zhang Xinyue Wang Na FengTiecheng Wang Yongkun Zhao Hang Chi Feihu Yan Xianzhu Xia Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100021China Changchun Veterinary Research Institute Chinese Academy of Agricultural SciencesChangchun132122China Jiangsu Co-innovation Centre for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou225009China

The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency,which underscores the urgent need for universal therapeutic antibody intervention for clinical ***,we screened three alpacas-derived nanobodies(Nbs)with neutralizing activity from twenty RBD-specific *** three Nbs were fused with the Fc domain of human IgG,namely aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc,which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to *** effectively neutralized SARS-CoV-2 pseudoviruses D614G,Alpha,Beta,Gamma,Delta,and Omicron sub-lineages BA.1,BA.2,BA.4,and BA.5 and authentic SARS-CoV-2 prototype,Delta,and Omicron BA.1,BA.2 *** mice-adapted COVID-19 severe model,intranasal administration of aVHH-11-Fc,aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory *** the COVID-19 mild model,aVHH-13-Fc,which represents the optimal neutralizing activity among the above three Nbs,effectively protected hamsters from the challenge of SARS-CoV-2 prototype,Delta,Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the *** structural modeling of aVHH-13 and RBD,aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved *** together,our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2,including those Delta and Omicron variants which have evolved into global pandemic strains.

关键词： COVID-19 SARS-CoV-2 Nanobody Broad-spectrum Therapeutic rodent models

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rodent models and metabolomics in non-alcoholic fatty liver disease: What can we learn?

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World Journal of Hepatology 2022年第2期14卷 304-318页

作者： Maria Martin-Grau Vannina G Marrachelli Daniel Monleon Department of Pathology University of ValenciaValencia 46010Spain Department of Physiology University of ValenciaValencia 46010Spain Health Research Institute INCLIVA Valencia 46010Spain CIBER de Fragilidad y Envejecimiento Saludable(CIBERfes) Madrid 28029Spain

Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s *** is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis,which can progress to *** molecular and metabolic changes are required for the hepatocyte to finally vary its function;hence a“multiple hit”hypothesis seems a more accurate *** studies and current knowledge suggest that in most cases,NAFLD initiates and progresses through most of nine hallmarks of the disease,although the triggers and mechanisms for these can vary *** use of animal models remains crucial for understanding the disease and for developing tools based on biological *** certain requirements to be met,a good model must imitate certain aspects of the human NAFLD disorder,be reliable and reproducible,have low mortality,and be compatible with a simple and feasible *** studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the *** seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological *** this review,we provide a brief introduction to NAFLD hallmarks,the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.

关键词： Non-alcoholic fatty liver disease Liver disease rodent models Metabolic profiling Metabolomics Biomarkers

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Determinants of uterine aging:lessons from rodent models

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Science China(Life Sciences) 2012年第8期55卷 687-693页

作者： KONG ShuangBo ZHANG Shuang CHEN YongJie WANG WeiXiang WANG BingYan CHEN Qi DUAN EnKui WANG HaiBin State Key Laboratory of Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Graduate University of Chinese Academy of Sciences Beijing 100039China

The uterus is an indispensable organ for the development of a new life in eutherian *** female mammalian reproductive capacity diminishes with *** this respect,the senescence of uterine endometrium is convinced to contribute to this *** review focuses on the physiological function of the uterus and the related influence of aging mainly in rodent models.A better understanding of the underlying mechanisms governing the process of uterine aging is hoped to generate new strategies to prolong the reproductive lifespan in humans.

关键词： determinants uterine aging rodent models

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Recent Advances in Animal models of Zika Virus Infection

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Virologica Sinica 2018年第2期33卷 125-130页

作者： Shupeng Dong Qiming Liang Shanghai Institute of Immunology Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine

An infection by Zika virus(ZIKV), a mosquito-borne flavivirus, broke out in South American regions in 2015, and recently showed a tendency of spreading to North America and even worldwide. ZIKV was first detected in 1947 and only 14 human infection cases were reported until 2007. This virus was previously observed to cause only mild flu-like ***, recent ZIKV infections might be responsible for the increasing cases of neurological disorders such as GuillainBarre′ syndrome and congenital defects, including newborn microcephaly. Therefore, researchers have established several animal models to study ZIKV transmission and pathogenesis, and test therapeutic candidates. This review mainly summarizes the reported animal models of ZIKV infection, including mice and non-human primates.

关键词： Zika virus Flavivirus rodent models Non-human primate models

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Mechanisms and treatment strategies of demyelinating and dysmyelinating Charcot-Marie-Tooth disease

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Neural Regeneration Research 2023年第9期18卷 1931-1939页

作者： Nadège Hertzog Claire Jacob Faculty of Biology Institute of Developmental Biology and NeurobiologyJohannes Gutenberg University MainzHanns-Dieter-Hüsch-WegMainzGermany

Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin *** is of paramount importance for axonal integrity and fast axon potential ***,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth ***-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as *** demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,*** resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected *** treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment *** this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.

关键词： Charcot-Marie-Tooth disease rodent models emerging treatments demyelination and dysmyelination endoplasmic reticulum stress gene therapy myelin repair Schwann cells unfolded protein response

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