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黄芩苷对SARS-COV-2侵袭的抑制作用研究
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作者 耿雪 王雪 +3 位作者 周倩 苏昕宇 李水仙 祝清芬 《药学研究》 CAS 2024年第4期333-337,共5页
目的在体外研究黄芩苷对新型冠状病毒(SARS-CoV-2)入侵细胞过程的抑制作用。方法利用构建有荧光素酶报告基因的SARS-CoV-2 S蛋白假病毒系统,通过荧光素酶试剂盒检测加入黄芩苷和假病毒后Huh-7细胞中的荧光素表达变化,进而绘制病毒抑制... 目的在体外研究黄芩苷对新型冠状病毒(SARS-CoV-2)入侵细胞过程的抑制作用。方法利用构建有荧光素酶报告基因的SARS-CoV-2 S蛋白假病毒系统,通过荧光素酶试剂盒检测加入黄芩苷和假病毒后Huh-7细胞中的荧光素表达变化,进而绘制病毒抑制曲线。结果黄芩苷能显著抑制Huh-7细胞的病毒感染率,黄芩苷和病毒提前共孵育组与直接加入组在不同浓度下的病毒抑制曲线并无显著差别,表明黄芩苷并不能与病毒直接结合,而是通过作用于病毒S蛋白介导的细胞融合过程产生抑制作用;黄芩苷在0.125 mg·mL^(-1)浓度时,对病毒的抑制率在4 h组显著降低,在0 h和2 h组并无显著差别,表明黄芩苷可能在病毒入侵细胞(非吸附)阶段产生抑制作用,且介导的入侵抑制阶段发生在4 h内。结论黄芩苷可能通过介导抑制SARS-CoV-2病毒S蛋白与细胞表面受体的融合过程,在非吸附阶段抑制病毒的入侵,发挥抗新冠病毒活性。 展开更多
关键词 黄芩苷 新型冠状病毒 荧光素酶检测 sars-cov-2 s蛋白
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SARS-CoV-2 S蛋白引起呼吸道上皮细胞炎症反应的研究进展
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作者 刘兴健 张华华 张锐钢 《中国感染控制杂志》 CAS CSCD 北大核心 2024年第1期112-118,共7页
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染引起的肺炎对人类生命健康产生威胁,对社会经济造成巨大损失。病毒的结构蛋白刺突蛋白(S蛋白)一直被认为主要介导病毒侵入宿主细胞。S蛋白可独立于病毒引起多种细胞产生炎症反应,因此,了... 严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染引起的肺炎对人类生命健康产生威胁,对社会经济造成巨大损失。病毒的结构蛋白刺突蛋白(S蛋白)一直被认为主要介导病毒侵入宿主细胞。S蛋白可独立于病毒引起多种细胞产生炎症反应,因此,了解S蛋白本身对呼吸道的影响能够为防治新型冠状病毒感染提供新视角。本文对SARS-CoV-2结构蛋白S蛋白引起呼吸道上皮细胞炎症反应的可能机制、临床表现等方面的研究进展进行了梳理,以期为疾病的预防和治疗提供参考。 展开更多
关键词 sars-cov-2 s蛋白 ACE2 呼吸道炎症
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用于中和抗体评价和进入抑制剂筛选的多变异株SARS-CoV-2假病毒体系构建与评估
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作者 李静璇 刘峰 +3 位作者 王莹 程军平 肖智勇 周文霞 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第4期811-817,共7页
目的:构建一种高滴度SARS-CoV-2假病毒(PsV)体系,用于中和抗体体外评价与病毒进入抑制剂的筛选。方法:共转染慢病毒载体质粒psPAX2、pCDH-Luc与SARS-CoV-2 Spike(S)蛋白表达质粒,收获的假病毒上清感染ACE2-293T细胞。通过测定p24蛋白含... 目的:构建一种高滴度SARS-CoV-2假病毒(PsV)体系,用于中和抗体体外评价与病毒进入抑制剂的筛选。方法:共转染慢病毒载体质粒psPAX2、pCDH-Luc与SARS-CoV-2 Spike(S)蛋白表达质粒,收获的假病毒上清感染ACE2-293T细胞。通过测定p24蛋白含量反映PsV滴度,Western blot检测S蛋白在PsV中的表达。利用原始株、D614G、Gamma、Delta、Omicron PsV亚型对1株S蛋白单克隆抗体的中和能力进行评价。采用两种已报道的病毒进入抑制剂氯喹、角叉菜胶检测对Omicron PsV进入的影响。结果:慢病毒载体成功掺入了S蛋白,Western blot结果显示665Y位突变的S蛋白表现出与野生型全长S蛋白(180 kD)不同的切割形式(90 kD)。三质粒体系包装出的PsV滴度更高,S蛋白表达质粒、转移质粒与包装质粒比例在1∶3∶3时为原始株PsV包装的最佳条件。该条件下包装出的5种PsV滴度均在20 ng/ml以上。PsV可有效感染ACE2-293T细胞,双报告基因GFP与萤火虫荧光素酶表达明显,化学发光数值高达106。基于原始株S蛋白的单克隆抗体可有效中和原始株PsV,对原始株PsV的中和作用是对变异株PsV的10~30倍。病毒进入抑制剂氯喹与ι-角叉菜胶可显著抑制Omicron PsV进入宿主细胞。结论:成功构建了高滴度的SARS-CoV-2 PsV进入体系,该体系以荧光素酶报告基因为指示,包含原始株和D614G、PsV Gamma、Delta、Omicron 4种变异株PsV,可有效评价中和抗体与病毒进入抑制剂活性,区分二者对不同变异株的敏感性差异对抗SARS-CoV-2药物研发有重要意义。 展开更多
关键词 sars-cov-2 假病毒 s蛋白 中和抗体 病毒进入抑制剂
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SARS-CoV-2 S蛋白主要结构与突变及S蛋白引起疾病的潜在机制
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作者 刘兴健 张锐钢 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第4期857-861,共5页
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)对人类生命健康构成威胁,备受研究者的关注。研究发现,病毒的刺突蛋白(S蛋白)被认为是病毒感染的关键结构蛋白,该蛋白与靶细胞受体结合导致组织器官发生炎症反应。因此研究S蛋白引起疾病的潜... 严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)对人类生命健康构成威胁,备受研究者的关注。研究发现,病毒的刺突蛋白(S蛋白)被认为是病毒感染的关键结构蛋白,该蛋白与靶细胞受体结合导致组织器官发生炎症反应。因此研究S蛋白引起疾病的潜在机制对于疾病的治疗至关重要,然而病毒的演变进化给研究工作增加了一定的难度。本文总结了SARS-CoV-2 S蛋白的主要结构以及从Alpha到Omicron突变,及其引起多种疾病的潜在机制,从而为疾病的预防和治疗提供参考。 展开更多
关键词 sars-cov-2 s蛋白 ACE2 呼吸道炎症
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Roles of host proteases in the entry of SARS-CoV-2
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作者 Alexandria Zabiegalal Yunjeong Kim Kyeong-Ok Chang 《Animal Diseases》 CAS 2024年第1期27-39,共13页
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... 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. 展开更多
关键词 sars-cov-2 spike protein(s) Host proteases Cleavage site Virus entry
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一种吡唑并吡啶酮类衍生物对新型冠状病毒SARS-CoV-2的抑制作用研究
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作者 李银燕 姜琳瑞 +3 位作者 陈至烜 梁锦龙 何晓雪 杨洁 《沈阳药科大学学报》 CAS CSCD 2024年第7期914-921,共8页
目的探究3-(4-氯苯基)-1,4-二苯基-1,4,5,7-四氢-6H-吡唑并[3,4-b]吡啶-6-酮(以下简称为J1)体外抑制新型冠状病毒(SARS-CoV-2)的作用及潜在作用机制。方法采用MTT法评价化合物J1对Vero-E6、ACE2/293T和HRT18细胞的毒性。利用感染性SARS-... 目的探究3-(4-氯苯基)-1,4-二苯基-1,4,5,7-四氢-6H-吡唑并[3,4-b]吡啶-6-酮(以下简称为J1)体外抑制新型冠状病毒(SARS-CoV-2)的作用及潜在作用机制。方法采用MTT法评价化合物J1对Vero-E6、ACE2/293T和HRT18细胞的毒性。利用感染性SARS-CoV-2和人冠状病毒OC43(HCoV-OC43)检测化合物J1的抗冠状病毒活性。采用SARS-CoV-2假病毒体外细胞感染模型和时间点加药实验检测J1抑制SARS-CoV-2病毒感染靶细胞的作用阶段。通过S蛋白介导的细胞融合抑制实验检测J1是否通过阻止病毒膜融合而抑制SARS-CoV-2的进入。采用SPR实验和分子对接技术阐明J1与SARS-CoV-2 S蛋白的作用。结果J1对Vero-E6、ACE2/293T和HRT18细胞的毒性较小,半数细胞毒性浓度CC50均大于100μmol·L^(-1)。J1能显著抑制SARS-CoV-2原始株和Delta变异株的活性,半数有效浓度EC50分别为607μmol·L^(-1)和221μmol·L^(-1)。此外,J1可抑制HCoV-OC43病毒的感染,显著减少NP蛋白和mRNA的表达。分子对接结果显示,J1通过氢键作用和疏水作用力与SARS-CoV-2 S蛋白活性位点稳定结合。机制研究结果表明,J1可抑制SARS-CoV-2病毒进入靶细胞,半数抑制浓度IC50为157μmol·L^(-1)。J1浓度依赖性抑制SARS-CoV-2 S蛋白介导的细胞-细胞膜融合,SPR实验证实J1与S蛋白具有较强结合能力。结论吡唑并吡啶酮类衍生物J1通过靶向S蛋白抑制SARS-CoV-2进入靶细胞。 展开更多
关键词 sars-cov-2 s 蛋白 抗冠状病毒药物 小分子化合物 进入抑制剂
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抗SARS-CoV-2 S蛋白纳米抗体的筛选、表达和鉴定
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作者 蒋丹 舒纬童 +3 位作者 李光琪 蓝华滔 黄倩莹 徐广贤 《免疫学杂志》 CAS CSCD 2024年第3期309-314,共6页
目的筛选特异性抗SARS-CoV-2 S蛋白纳米抗体序列,表达纯化重组抗SARS-CoV-2纳米抗体,评估其特性及应用潜能。方法基于前期构建的天然噬菌体纳米抗体展示库,以生物素化SARS-CoV-2 S蛋白受体结合结构域抗原为靶点,利用生物素-链霉亲和素... 目的筛选特异性抗SARS-CoV-2 S蛋白纳米抗体序列,表达纯化重组抗SARS-CoV-2纳米抗体,评估其特性及应用潜能。方法基于前期构建的天然噬菌体纳米抗体展示库,以生物素化SARS-CoV-2 S蛋白受体结合结构域抗原为靶点,利用生物素-链霉亲和素液相筛选法、噬菌体-ELISA和测序筛选抗SARS-CoV-2 S蛋白纳米抗体序列;构建重组抗SARS-CoV-2 S蛋白纳米抗体表达载体,IPTG诱导表达并纯化,采用SDS-PAGE、Western blot和ELISA分析其特征及应用潜能。结果成功获得2条抗SARS-CoV-2 S蛋白纳米抗体序列,并构建了相应原核表达菌;成功表达纯化重组抗SARS-CoV-2 S蛋白纳米抗体,其与SARS-CoV-2 S蛋白可特异性结合。结论筛选及表达的重组抗SARS-CoV-2 S蛋白纳米抗体为其应用于SARS-CoV-2检测和治疗及相关研究提供基础。 展开更多
关键词 纳米抗体 新型冠状病毒(sars-cov-2)s蛋白 纯化表达
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To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant
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作者 Pooja Patel Yogita Mistry +1 位作者 Monika Patel Summaiya Mullan 《Advances in Microbiology》 CAS 2024年第5期247-255,共9页
Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the... Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community. 展开更多
关键词 sars-cov-2 s Gene Target Failure Whole Genome sequencing Omicron
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Accurate Diagnosis of SARS-CoV-2 JN.1 by Sanger Sequencing of Receptor-Binding Domain Is Needed for Clinical Evaluation of Its Immune Evasion
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作者 Sin Hang Lee 《Journal of Biosciences and Medicines》 2024年第4期69-78,共10页
Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation... Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies. 展开更多
关键词 Omicron JN.1 sars-cov-2 sanger sequencing RBD L455s Mutation Immune Evasion Vaccination Policies CDC
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Highly Sensitive Poly-N-isopropylacrylamide Microgel-based Electrochemical Biosensor for the Detection of SARS-COV-2 Spike Protein
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作者 CHEN Hao HOU Zhi Yuan +5 位作者 CHEN Die LI Ting WANG Yi Ming DE LIMA Marcelo Andrade YANG Ying GUO Zhen Zhong 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2023年第3期269-278,共10页
Objective Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019(COVID-19),a new,highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).... Objective Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019(COVID-19),a new,highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,considerable attention has been paid to the development of new diagnostic tools for the early detection of SARS-CoV-2.Methods In this study,a new poly-N-isopropylacrylamide microgel-based electrochemical sensor was explored to detect the SARS-CoV-2 spike protein(S protein)in human saliva.The microgel was composed of a copolymer of N-isopropylacrylamide and acrylic acid,and gold nanoparticles were encapsulated within the microgel through facile and economical fabrication.The electrochemical performance of the sensor was evaluated through differential pulse voltammetry.Results Under optimal experimental conditions,the linear range of the sensor was 10-13-10-9 mg/m L,whereas the detection limit was 9.55 fg/mL.Furthermore,the S protein was instilled in artificial saliva as the infected human saliva model,and the sensing platform showed satisfactory detection capability.Conclusion The sensing platform exhibited excellent specificity and sensitivity in detecting spike protein,indicating its potential application for the time-saving and inexpensive detection of SARS-CoV-2. 展开更多
关键词 MICROGEL sars-cov-2 spike protein DETECTION
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AR、SKP2、SOX10、PD-L1及TIL表达在三阴性乳腺癌中的意义
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作者 刘娟 殷丽娟 范德生 《诊断学理论与实践》 2024年第2期162-172,共11页
目的:探索雄激素受体(androgen receptor,AR)、S期激酶相关蛋白2(S-phase kinase-associated protein 2,SKP2)、性别决定区Y相关的HMG盒含因子10(sry-related HMG box-containing factor 10,SOX10)、程序性死亡配体1(programmed death-l... 目的:探索雄激素受体(androgen receptor,AR)、S期激酶相关蛋白2(S-phase kinase-associated protein 2,SKP2)、性别决定区Y相关的HMG盒含因子10(sry-related HMG box-containing factor 10,SOX10)、程序性死亡配体1(programmed death-ligand 1,PD-L1)及肿瘤浸润性淋巴细胞(tumor infiltrating lymphocyte,TIL)在三阴性乳腺癌(triple negative breast cancer,TNBC)表达与临床病理特征和预后的关系。方法:根据苏木精-伊红染色(hematoxylineosin, HE)染色切片评判109例TNBC瘤巢内TIL的比例,采用Leica Bond-Max全自动免疫组化仪检测TNBC组织中AR、SKP2、SOX10、PD-L1的表达。分析以上各生物指标与临床病理特征间的关系,并采用kaplan-Meier、Log-rank进行生存分析。结果:95例患者获得随访,中位随访时间为48个月,中位无病生存时间(disease-free survival, DFS)为42个月,中位总生存时间(overall survival, OS)48个月。在TNBC中,AR阳性表达与淋巴结转移阴性(P=0.009)、肿瘤最大径<2 cm(P=0.008)相关,TIL高表达与低级别TNBC相关(P=0.007),SKP2阳性表达与神经/脉管侵犯阳性(P=0.011)、高级别TNBC相关(P=0.002),SOX10阳性表达与淋巴结转移阳性(P=0.022)、高级别TNBC(P=0.005)相关,PD-L1阳性表达与淋巴结转移阳性(P=0.020)、神经/脉管侵犯阳性(P=0.006)、高级别TNBC(P=0.042)相关。生存分析显示,SKP2、SOX10阳性表达与更差的DFS(P=0.007、P<0.001)和OS(P=0.013、P<0.001)相关,TIL高表达与更好的DFS(P=0.016)及OS(P=0.004)相关。在生物表志物的联合表达中,AR+/SKP2-、AR+/SOX10-与更好的DFS(P=0.004、P<0.001)及OS(P=0.007、P=0.001)相关,SOX10+/低TIL、PD-L1+/低TIL与更差的DFS(P<0.001、P=0.008)及OS(P=0.001、P=0.002)相关,AR-/低TIL者具有更差的OS(P=0.014)。SKP2(HR=4.143,95%CI为1.578~10.875)、SOX10(HR=7.578,95%CI为2.067~27.782)的阳性表达是影响TNBC患者DFS的独立预后因子,SKP2(HR=3.758,95%CI为1.400~10.084)、SOX10(HR=5.131,95%CI为1.316~20.000)及TIL(HR=0.375,95%CI为0.154~0.917)的阳性表达是TNBC患者OS的独立预后因子(P均<0.05)。结论:在TNBC中,AR阳性、TIL高表达与具有更好预后的临床病理特征相关,SKP2、SOX10和PD-L1与具侵袭性的临床病理特征相关。SKP2、SOX10及TIL表达与TNBC预后相关,提示这些生物指标可能成为TNBC新的预后因子,同时它们也有可能成为潜在的治疗靶点。 展开更多
关键词 三阴性乳腺癌 雄激素受体 s期激酶相关蛋白2 性别决定区Y相关的HMG盒含因子10 程序性死亡配体1 肿瘤浸润性淋巴细胞
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A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease 被引量:2
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作者 Yongjiang Zhang Shiyi Yin +4 位作者 Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1828-1834,共7页
Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the m... Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin. 展开更多
关键词 endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 MITOPHAGY oxidative stress PARKIN Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2
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帕金森病患者血清LCN2、PROS1水平变化及其与疾病分期、认知障碍的相关性
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作者 单树崇 吴召军 何清 《国际检验医学杂志》 CAS 2024年第9期1068-1072,1079,共6页
目的探讨帕金森病(PD)患者血清脂质运载蛋白2(LCN2)、蛋白S基因(PROS1)水平变化及其与疾病分期、认知障碍的相关性。方法选取2019年1月至2022年12月该院诊治的PD患者120例为研究对象(PD组),参考改良版Hoehn-Yahr分级(H-Y分级),分为早期P... 目的探讨帕金森病(PD)患者血清脂质运载蛋白2(LCN2)、蛋白S基因(PROS1)水平变化及其与疾病分期、认知障碍的相关性。方法选取2019年1月至2022年12月该院诊治的PD患者120例为研究对象(PD组),参考改良版Hoehn-Yahr分级(H-Y分级),分为早期PD组(0~1.5级,n=50),中期PD组(>1.5~3.0级,n=39),晚期PD组(>3.0~5.0级,n=31)。以同期健康体检的60例体检健康者为对照组。检测两组血清LCN2、PROS1水平。比较不同PD疾病分期PD患者血清LCN2、PROS1水平差异。Spearman秩相关分析血清LCN2、PROS1水平与简易智力状态检查量表(MMSE),蒙特利尔认知评估量表(MoCA)及H-Y分级的相关性。多因素Logistic回归分析影响PD患者认知功能障碍的相关因素。绘制受试者工作特征(ROC)曲线分析血清LCN2、PROS1水平对PD患者认知障碍的评估价值。结果PD组血清LCN2、PROS1水平分别为(97.47±11.28)μg/L、(77.52±8.69)μg/L,明显高于对照组(40.15±6.22)μg/L、(32.49±4.37)μg/L,差异均有统计学意义(t=36.641、37.783,均P<0.05)。晚期PD组血清LCN2、PROS1水平高于早期、中期PD组,差异均有统计学意义(均P<0.05)。认知障碍组PD患者病程、血清LCN2、PROS1、H-Y分级均高于认知正常组患者,而MoCA评分、MMSE评分低于认知正常组,差异均有统计学意义(P<0.05)。血清LCN2、PROS1水平与MoCA评分,MMSE评分呈负相关(r=-0.634、-0.489,均P<0.05),与H-Y分级呈正相关(r=0.467、0.625,均P<0.05)。血清LCN2、PROS1是影响PD患者认知功能障碍的相关危险因素。血清LCN2、PROS1单独及联合对PD患者认知功能障碍预测的曲线下面积(AUC)为0.905(95%CI:0.868~0.955),0.803(95%CI:0.764~0.849),0.836(95%CI:0.770~0.867),血清LCN2、PROS1联合检测AUC明显高于单独检测,差异具有统计学意义(Z=5.558,4.974,均P<0.001)。结论PD患者血清LCN2、PROS1水平升高,与PD疾病分期、认知障碍有关,两者联合检测对PD患者认知障碍具有较高的评估价值。 展开更多
关键词 帕金森病 脂质运载蛋白2 蛋白s基因 疾病分期 认知功能障碍
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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白的B细胞及T细胞抗原表位的生物信息学分析 被引量:1
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作者 陶佳 李莎莎 +3 位作者 杨继辉 张婷瑞 吕咏雪 赵巍 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2023年第1期49-56,共8页
目的使用生物信息学方法预测严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白(S蛋白)的结构特点,并预测可能的B细胞和T细胞表位。方法从NCBI数据库中获取SARS-CoV-2的S蛋白氨基酸序列,通过蛋白质基本性质分析工具ProtParam分析S蛋白... 目的使用生物信息学方法预测严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白(S蛋白)的结构特点,并预测可能的B细胞和T细胞表位。方法从NCBI数据库中获取SARS-CoV-2的S蛋白氨基酸序列,通过蛋白质基本性质分析工具ProtParam分析S蛋白的理化性质;利用综合性序列工具软件Lasergene和蛋白质二级结构分析软件SOMPA分析S蛋白二级结构;蛋白质同源物/类似物Y识别引擎Phyre2和分子图像观察软件Rasmol构建并分析S蛋白三级结构;B细胞表位预测工具ABCpred、BepiPred和BcePred预测S蛋白的B细胞抗原表位;利用免疫表位数据库IEDB预测S蛋白的T细胞抗原表位。结果S蛋白由1273个氨基酸组成,理论等电点为6.24,原子组成为C_(6336)H_(9770)N_(1656)O_(1894)S_(54),属于稳定亲水性蛋白。Lasergene软件的Gramier-Robson方法预测显示:α螺旋占23.5%、β折叠占53.7%、转角区域占14.9%、无规则卷曲占8.33%;Lasergene软件的Chou-Fasman方法预测显示:α螺旋占20.9%,β折叠占35.5%,β转角占35.2%。同时,使用SOPMA在线服务工具分析S蛋白二级结构,其中α螺旋占28.59%,延长链占23.25%,β转角占3.38%,无规则卷曲占44.78%。ABCpred、BepiPred和BcePred分别预测S蛋白的潜在B细胞抗原表位数量为5个、11个、6个。IEDB预测的CD8^(+)T细胞表位和CD4^(+)T细胞表位结果中分别选择各人类白细胞抗原(HLA)基因型亲和力最好的5个表位。结论采用生物信息学方法预测SARS-CoV-2的S蛋白具有多个B细胞及T细胞抗原表位。 展开更多
关键词 严重急性呼吸综合征冠状病毒2(sars-cov-2) 刺突蛋白/s蛋白 生物信息学 B细胞表位 T细胞表位
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SARS-CoV-2突变株Omicron家族的演化传播和流行现状
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作者 郑嘉豪 王琼 +1 位作者 练仲豪 黄勋 《激光生物学报》 CAS 2023年第6期492-501,共10页
冠状病毒(CoV)属于套式病毒目冠状病毒科,为有包膜的单股正链RNA病毒,基因组约27~32 kb。近年来,冠状病毒对人类的生命健康造成了巨大的威胁,如2002年出现的严重急性呼吸综合征冠状病毒(SARSCoV)以及2012年出现的中东呼吸系统综合征冠... 冠状病毒(CoV)属于套式病毒目冠状病毒科,为有包膜的单股正链RNA病毒,基因组约27~32 kb。近年来,冠状病毒对人类的生命健康造成了巨大的威胁,如2002年出现的严重急性呼吸综合征冠状病毒(SARSCoV)以及2012年出现的中东呼吸系统综合征冠状病毒(MERS-CoV),特别是2019年出现并流行至今的严重急性呼吸综合征冠状病毒2(SARS-CoV-2),其在全世界范围内暴发,严重危害了人类健康和社会秩序,引发了人们的高度关注。迄今为止,SARS-CoV-2已经演化出了多个变体,且仍处于不断变异中。目前流行株型以Omicron为主,同时伴有其他多个变异型。当前我国新冠疫情防控已进入“乙类乙管”常态化防控阶段,SARS-CoV-2依然是未来一段时间内重要的公共卫生问题之一。本综述总结了SARS-CoV-2 Omicron主要株型的关键突变以及其与病毒传染致病、免疫逃逸等特性的关系,为了解SARS-CoV-2演化传播、流行现状等提供了参考。 展开更多
关键词 sars-cov-2 s蛋白 变异 感染致病 免疫逃逸
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SARS-CoV-2入胞机制的研究进展
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作者 袁小枚 李利峰 王嘉 《微生物前沿》 CAS 2023年第1期10-17,共8页
新冠病毒(SARS-CoV-2)大流行对全球的公共卫生及经济造成了前所未有的影响,有关它的研究也成为了当前科学界最热门的领域之一;作为病毒感染的首要环节,SARS-CoV-2的入胞机制更成为人们认识病毒行为、研究阻断病毒入侵途径的关注点。本文... 新冠病毒(SARS-CoV-2)大流行对全球的公共卫生及经济造成了前所未有的影响,有关它的研究也成为了当前科学界最热门的领域之一;作为病毒感染的首要环节,SARS-CoV-2的入胞机制更成为人们认识病毒行为、研究阻断病毒入侵途径的关注点。本文对SARS-CoV-2进入细胞过程中涉及的蛋白、受体、辅助因子、入胞过程中的S蛋白构象变化、入胞途径等进行了全面综述,以期展示SARS-CoV-2的入胞条件与动态图谱,为明晰病毒与细胞的相互作用、研制疫苗或治疗药物奠定基础。 展开更多
关键词 sars-cov-2 s蛋白 受体 水解激活 膜融合 入胞
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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疫苗研究进展
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作者 葛新斌 渠淇淦 +5 位作者 王泽光 张舜耕 池岩 单春慧 刘瑞寒 赵清 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2023年第10期946-951,共6页
2019冠状病毒病(COVID-19)是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引起的,SARS-CoV-2病毒毒株不断突变、进化。疫苗研究是控制COVID-19最直接、最有效的方式,根据制备机制不同,SARS-CoV-2疫苗分为灭活病毒疫苗、减毒活疫苗、mRN... 2019冠状病毒病(COVID-19)是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引起的,SARS-CoV-2病毒毒株不断突变、进化。疫苗研究是控制COVID-19最直接、最有效的方式,根据制备机制不同,SARS-CoV-2疫苗分为灭活病毒疫苗、减毒活疫苗、mRNA疫苗、DNA疫苗、病毒载体疫苗、病毒样颗粒疫苗和蛋白亚单位疫苗等。其中,病毒蛋白亚单位疫苗因其安全性、有效性高具有广泛应用前景,病毒核衣壳蛋白免疫原性高,可变性较低,可作为疫苗制备新方向。我们通过梳理SARS-CoV-2疫苗研究进展、疫苗安全性、疫苗免疫效率等方面,总结疫苗研究的发展现状,并提出可能的研制策略,以期为今后防疫工作提供参考。 展开更多
关键词 急性呼吸综合征冠状病毒2(sars-cov-2) 疫苗 s蛋白 综述
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Mutations in spike protein and allele variations in ACE2 impact targeted therapy strategies against SARS-CoV-2 被引量:1
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作者 Chuan-Jun Shu Xuan Huang +3 位作者 Hui-Hao Tang Ding-Ding Mo Jian-Wei Zhou Cheng Deng 《Zoological Research》 SCIE CAS CSCD 2021年第2期170-181,共12页
Coronavirus disease 2019(COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, how... Coronavirus disease 2019(COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2(ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-Co V-2. We analyzed clinical data, genetic data, and receptor binding capability.Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal reninangiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations(V354 F and V470 A) by receptorligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354 F and V470 A mutants has increased with the development of the SARS-Co V-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations. 展开更多
关键词 sars-cov-2 COVID-19 ACE2 spike protein Receptor-ligand docking Drug therapy
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<i>Morinda citrifolia</i>(Noni) Fruit Juice Inhibits SARS-CoV-2 Spike Protein Binding of Angiotensin-Converting Enzyme 2 (ACE2)
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作者 Brett J. West Shixin Deng 《Journal of Biosciences and Medicines》 2021年第11期42-51,共10页
COVID-19 is a global pandemic that has claimed millions of lives. This disease is caused by a coronavirus, SARS-CoV-2, which requires the binding of its spike protein to angiotensin-converting enzyme 2 (ACE2) for infe... COVID-19 is a global pandemic that has claimed millions of lives. This disease is caused by a coronavirus, SARS-CoV-2, which requires the binding of its spike protein to angiotensin-converting enzyme 2 (ACE2) for infection of the host cell. <em>Morinda citrifolia</em> (noni) fruit juice has antiviral activity that involves enhancement of immune system function. SARS-CoV-2 spike-ACE2 interaction experiments were carried out to further investigate the antiviral properties of noni juice and its major iridoids. Noni juice inhibited binding by approximately 69%. Scandoside was the most active of the three iridoids evaluated, reducing average spike protein-ACE2 interaction by 79.25%. The iridoids worked synergistically towards inhibiting spike protein binding when assayed together, improving activity by more than 22% above the expected level. But the modest activity of the most abundant iridoid, deacetylasperulosidic acid, indicates that other phytochemicals (<em>i.e</em>. scopoletin, quercetin, rutin and kaempferol) are also involved. Our results suggest that the presence of several biological active phytochemicals in noni juice enhances resistance to SARS-CoV-2 by interfering with its ability to bind ACE2. This is a new and significant anti-viral mechanism of noni juice that does not directly involve its immunomodulatory properties. 展开更多
关键词 CORONAVIRUs COVID-19 sars-cov-2 spike protein Morinda citrifolia NONI IRIDOID
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Universal COVID-19 Vaccine Targeting SARS-CoV-2 Envelope Protein
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作者 Chung-Min Tsai 《World Journal of Vaccines》 2021年第3期19-27,共9页
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused over 382 million cases and over 2.7 million deaths globally as of 23 March 2021. By ... The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused over 382 million cases and over 2.7 million deaths globally as of 23 March 2021. By that date, at least 10 SARS-CoV-2 variants had emerged. The transmissibility and lethality of the variants are higher than those of the Wuhan reference strain. Therefore, a universal vaccine for the reference strain and all variants (present and future) is indispensable. The coronavirus envelope (E) protein is an integral membrane protein crucial to the viral lifecycle and the pathogenesis of coronaviruses. The SARS-CoV-2 E protein has a postsynaptic density protein 95/Drosophila disc large tumor suppressor/zonula occludens-1 (PDZ) binding motif (PBM), and its interaction with PDZ-domain-2 of the human tight junction protein may interrupt the integrity of lung epithelium. Furthermore, the SARS-CoV-2 E protein itself is a homopentameric cation channel viroporin, which may be involved in viral release. This protein is thus a potential target for the development of a universal COVID-19 vaccine, because of its highly conserved amino acid sequence. The variant mutations occur mainly in the spike protein, and conservation of E protein remained in most Variants of Concern (VOC). Only one of the extant VOC have mutations in the E protein that P71L mutation occurs in the South African variant 501Y.V2 (B.1.351). If a vaccine is designed to target E protein, two scenarios are possible: 1) SARS-CoV-2 maintains a highly conserved E protein amino acid sequence, rendering the virus consistently or permanently susceptible to the vaccine;or 2) the E protein mutates and new variants evolve accordingly. In scenario 2, the tertiary structure and function of the E protein homopentameric cation channel viroporin, PBM, or other aspects affecting pathogenicity would be attenuated. Either scenario would thus ameliorate the pandemic. I therefore propose that a vaccine targeting the SARS-CoV-2 E protein would be effective against the Wuhan reference strain and all current and future SARS-CoV-2 variants. Efforts to create E protein-based vaccines are ongoing. Further research and clinical trials are needed to realize this universal COVID-19 vaccine. 展开更多
关键词 COVID-19 sars-cov-2 Envelope protein Universal COVID-19 Vaccine
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