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A novel bat coronavirus with a polybasic furin-like cleavage site

Virologica Sinica 2023年第3期38卷 344-350页

作者： Wentao Zhu Yuyuan Huang Jian Gong Lingzhi Dong Xiaojie Yu Haiyun Chen Dandan Li Libo Zhou Jing Yang Shan Lu Department of Infectious Diseases and Clinical Microbiology Beijing Institute of Respiratory Medicine and Beijing Chao-Yang HospitalCapital Medical UniversityBeijing100020China State Key Laboratory of Infectious Disease Prevention and Control National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Hainan Provincial Center for Disease Control and Prevention Haikou570203China Research Units of Discovery of Unknown Bacteria and Function Chinese Academy of Medical SciencesBeijing100730China

The current pandemic of COVID-19 caused by a novel coronavirus,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),threatens human health around the world.Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2;however,coronavirus ecology in bats is still nascent.Here,we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats,collected from Hainan Province,China.Three coronaviruses,namely bat betacoronavirus(Bat CoV)CD35,Bat CoV CD36 and bat alpha-coronavirus CD30 were identified.Bat CoV CD35 genome had 99.5%identity with Bat CoV CD36,both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013(71.4%),followed by SARS-CoV-2(54.0%).Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade,and together with Bat Hp-betacoronavirus Zhejiang2013,was basal to the lineage of SARS-CoV-1 and SARS-CoV-2.Notably,Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2.The furin cleavage sites between CD35 and CD36 are identical.In addition,the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2,especially in one binding loop.In conclusion,this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.

关键词： Bat Coronavirus SARS-CoV-2 Betacoronavirus Furin cleavage site

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Tau truncation in the pathogenesis of Alzheimer's disease: a narrative review

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Neural Regeneration Research 2024年第6期19卷 1221-1232页

作者： Dandan Chu Xingyue Yang Jing Wang Yan Zhou Jin-Hua Gu Jin Miao Feng Wu Fei Liu Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products Coinnovation Center of Neuroregeneration Nantong University 2. Department of Pharmacology School of Pharmacy Nantong University 3. Department of Biochemistry and Molecular Biology School of Medicine Nantong University 4. Department of Clinical Pharmacy Affiliated Maternity and Child Health Care Hospital of Nantong University Nantong University 5. Laboratory of Animal Center Nantong University Department of Neurochemistry Inge Grundke-Iqbal Research Floor New York State Institute for Basic Research in Developmental Disabilities

Alzheimer’s disease is characterized by two major neuropathological hallmarks—the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubuleassociated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer’s disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics. In addition, Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner. This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments, investigates the role of specific truncations in physiological and pathological states of Alzheimer’s disease, and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer’s disease.

关键词： Alzheimer's disease cleavage site diagnosis marker neurofibrillary tangles phosphorylation Tau Tau aggregation therapy truncation

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Combined insertion of basic and non-basic amino acids at hemagglutinin cleavage site of highly pathogenic H7N9 virus promotes replication and pathogenicity in chickens and mice

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Virologica Sinica 2022年第1期37卷 38-47页

作者： Aobaixue Zhou Jiahao Zhang Huanan Li Qiang Xu Yiqun Chen Bo Li Wanying Liu Guanming Su Xingxing Ren Guangjie Lao Baozheng Luo Ming Liao Wenbao Qi College of Veterinary Medicine South China Agricultural UniversityGuangzhou510642China National Avian Infiuenza Para-reference Laboratory South China Agricultural UniversityGuangzhou510642China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou510642China Gongbei Customs Technology Center Zhuhai519000China National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control Guangzhou510642China Key Laboratory of Zoonoses Ministry of AgricultureGuangzhou510642China Key Laboratory of Animal Vaccine Development Ministry of AgricultureGuangzhou510642China Key Laboratory of Zoonoses Prevention and Control of Guangdong Province Guangzhou510642China

Since mid-2016,the low pathogenic H7N9 influenza virus has evolved into a highly pathogenic(HP)phenotype in China,raising many concerns about public health and poultry industry.The insertion of a“KRTA”motif at hemagglutinin cleavage site(HACS)occurred in the early stage of HP H7N9 variants.During the co-circulation,the HACS of HP-H7N9 variants were more polymorphic in birds and humans.Although HP-H7N9 variants,unlike the H5 subtype virus,exhibited the insertions of basic and non-basic amino acids,the underlying function of those insertions and substitutions remains unclear.The results of bioinformatics analysis indicated that the PEVPKRKRTAR/G motif of HACS had become the dominant motif in China.Then,we generated six H7N9 viruses bearing the PEIPKGR/G,PEVPKGR/G,PEVPKRKRTAR/G,PEVPKGKRTAR/G,PEVPKGKRIAR/G,and PEVPKRKRR/G motifs.Interestingly,after the deletion of threonine and alanine(TA)at HACS,the H7N9 viruses manifested decreased thermostability and virulence in mice,and the PEVPKRKRTAR/G-motif virus is prevalent in birds and humans probably due to its increased transmissibility and moderate virulence.By contrast,the insertion of non-basic amino acid isoleucine and alanine(IA)decreased the transmissibility in chickens and virulence in mice.Remarkably,the I335V substitution of H7N9 virus enhanced infectivity and transmission in chickens,suggesting that the combination of mutations and insertions of amino acids at the HACS promoted replication and pathogenicity in chickens and mice.The ongoing evolution of H7N9 increasingly threatens public health and poultry industry,so,its comprehensive surveillance and prevention of H7N9 viruses should be pursued.

关键词： H7N9 Highly pathogenic cleavage site Basic and non-basic amino acids Pathogenicity

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Roles of host proteases in the entry of SARS-CoV-2

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Animal Diseases 2024年第1期4卷 27-39页

作者： Alexandria Zabiegalal Yunjeong Kim Kyeong-Ok Chang Department of Diagnostic Medicine and Pathobiology College of Veterinary MedicineKansas State University1800 Denison Avenue ManhattanKS 66506USA

The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.

关键词： SARS-CoV-2 Spike protein(S) Host proteases cleavage site Virus entry

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A combined method based on wavelet transform for signal Peptide Local Features Recognition

A combined method based on wavelet transform for signal Pept...

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第九届全国计算（机）化学学术会议

作者： Yizhou Li Cuisong Zhou Zhining Wen Fuyuan Tan Menglong Li College of Chemistry,Sichuan University,Sichuan,Chengdu,610064,

＜正＞Signal peptides direct nascent proteins to certain organelles and are cleaved off after the proteins transported.With the rapid increase of sequence entries,it is highly desirable to develop automated algorithm to identify the signal peptide or predict its cleavage site.Thus,many methods have been developed.The vast majority of existing predictive methods resorted to a fixed window pattern,commonly.For example,weight-matrix,an early computational method for predicting cleavage sites,employed a so-called summation window of（-13,+2）to predict cleavage sites of both eukaryotic and prokaryotic.A predictor SignalP was developed for both signal peptide and its cleavage site based on neural network.It applied different window patterns to five datasets:（-15, 4-4）to human,（-17,+2）to eukaryote,（-11,+2）to Gram-negative bacteria,（-21,+2）to Gram-positive bacteria and（-15,+2）to E.coll.It prompts us to propose a model that is universal for all signal peptides. The properties of signal peptides are known to differ between various types of organisms, including the length and constituent.It has been reported that the location of cleavage sites are related to several local featUres in signal peptides.In this context,studies on these local features might be helpful for constructing such a model and,even,for the further researches on signal peptides.To construct such a model,it shall firstly encounter the problem that signal peptides are various in different organism types.As a solution to this,the architecture of the model is separated into two parts.In the first step,h-region is detected.Following this,the last three characteristic amino acids（Here,we call it（-3,-1）segment）of each signal peptide is recognized.In the submodel of detecting h-region,a strategy of two-reconstructed profiles with wavelet transform was proposed.It is well performed and demonstrated not affected by the variety of h-regious. This combined model is convenient to different organism types.When predicting h-region,the accuracy of 96.9% is achieved.The detec

关键词： Signal Peptide cleavage site Wavelet Transform

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