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1三种强致病性冠状病毒与人蛋白质相互作用研究进展显示文摘2019年12月,新型冠状病毒SARS-CoV-2引起的呼吸道疾病在中国武汉暴发并迅速席卷全球。截至2020年7月7日,在全球范围内感染人数超过1150万,死亡人数达到53万。导致严重疾病的冠状病毒还包括SARS-CoV和MERS-CoV。SARS-CoV-2与SARS-CoV在致病性、基因组和蛋白质组结构上高度同源,其感染及发病机制亦有较高的相似性。针对以上三种冠状病毒引起的呼吸道疾病临床上尚无有效的药物和疫苗,其中一个重要原因是对冠状病毒基本生物学机制的理解尚不充分。蛋白质在病毒的致病过程中发挥了重要作用,研究病毒与宿主的蛋白质相互作用有助于深入了解病毒的致病机制,为开发预防和治疗病毒感染的有效疫苗和高效药物提供指引。本文综述了SARS-CoV-2、SARSCoV及MERS-CoV三种冠状病毒蛋白与宿主蛋白的相互作用、病毒自身蛋白的相互作用,以及这些蛋白质相互作用所发挥的功能,如转录翻译、病毒组装、抑制免疫反应等,以期对SARS-CoV-2的机制研究及药物开发提供参考。郑云萧 江何伟 陶生策 2020生命的化学2020,40,8:7
2Structural biology of SARS-CoV-2:open the door for novel therapies显示文摘Severe Acute Respiratory Syndrome Coronavirus-2(SARS-CoV-2)is the causative agent of the pandemic disease COVID-19,which is so far without efficacious treatment.The discovery of therapy reagents for treating COVID-19 are urgently needed,and the structures of the potential drug-target proteins in the viral life cycle are particularly important.SARS-CoV-2,a member of the Orthocoronavirinae subfamily containing the largest RNA genome,encodes 29 proteins including nonstructural,structural and accessory proteins which are involved in viral adsorption,entry and uncoating,nucleic acid replication and transcription,assembly and release,etc.These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities.This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis,providing insights into the mechanisms underlying viral infection,prevention of infection,and treatment.Indeed,these studies open the door for COVID therapies,leading to ways to prevent and treat COVID-19,especially,treatment of the disease caused by the viral variants are imperative.Weizhu Yan Yanhui Zheng Xiaotao Zeng Bin He Wei Cheng 2022Signal Transduction and Targeted Therapy2022,7,2:2
3HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19显示文摘Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)is a major pathological feature of Coronavirus Disease 2019(COVID-19)and a crucial determinant in COVID-19 prognosis.Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control.Here,we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α(HIF-1α)play key roles in the virus infection and pro-inflammatory responses.Mingfu Tian Weiyong Liu Xiang Li Peiyi Zhao Muhammad Adnan Shereen Chengliang Zhu Shanyu Huang Siyu Liu Xiao Yu Miaomiao Yue Pan Pan Wenbiao Wang Yongkui Li Xulin Chen Kailang Wu Zhen Luo Qiwei Zhang Jianguo Wu 2021Signal Transduction and Targeted Therapy2021,6,9:1
4Pro-inflammatory microenvironment and systemic accumulation of CXCR3+cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2显示文摘Understanding the pathological features of severe acute respiratory syn drome coronavirus 2(SARS-CoV-2)infect io n in an animal model is crucial for the treatment of coronavirus disease 2019(COVID-19).Here,we compared imnnunopathological changes in young and old rhesus macaques(RMs)before and after SARS-CoV-2 infection at the tissue level.Quantitative analysis of multiplex immunofluoresce nee staining images of formali n-fixed paraffi n-embedded(FFPE)sections showed that SARS-CoV-2 infectio n specifically induced elevated levels of apoptosis,autophagy,and nuclear factor kappa-B(NF-kB)activation of angiotensirv convert!ng enzyme 2(ACE2)+cells,and increased interferon a(IFN-a)-and interleukin 6(IL-6)-secreting cells and C-X-C motif chemokine receptor 3(CXCR3)+cells in lung tissue of old RMs.This pathological pattern,which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens,was significantly correlated with the systemic accumulation of CXCR3+cells in lungs,spleens,and peripheral blood.Furthermore,the ratio of CXCR3+to T-box protein expression in T cell(T-bet)+(CXCR3+/T-bet+ratio)in CD8+cells may be used as a predictor of severe COVID-19.These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+cells in predicting severe COVID-19.Hong-Yi Zheng Xiao-Yan He Wei Li Tian-Zhang Song Jian-Bao Han Xiang Yang Feng-Liang Liu Rong-Hua Luo Ren-Rong Tian Xiao-Li Feng Yu-Hua Ma Chao Liu Ming-Hua Li Yong-Tang Zheng 2021Signal Transduction and Targeted Therapy2021,6,10:1
5病毒感染对细胞凋亡影响的研究进展显示文摘病毒感染与宿主细胞凋亡之间存在着密切的关系。宿主细胞主动性凋亡引起被感染细胞死亡,同时达到清除病毒的效果,在机体防御病毒感染中起重要作用;病毒亦主动诱导或抑制宿主细胞凋亡,从而达到在机体内复制产生更多子代病毒并完成生活周期的目的,并造成持续性感染或肿瘤发生。本文对细胞凋亡与病毒感染关系相关研究进行综述,为病毒感染性疾病的发病机制、治疗和抗病毒制剂研究提供新思路。杨筱萌 罗语思 张科 2022热带病与寄生虫学2022,20,5:1
6Cell deaths:Involvement in the pathogenesis and intervention therapy of COVID-19显示文摘The current pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection has dramatically influenced various aspects of the world.It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies to prevent and treat this threatening disease.It is universally acknowledged that cell death and cell autophagy are essential and crucial to maintaining host homeostasis and participating in disease pathogenesis.At present,more than twenty different types of cell death have been discovered,some parts of which have been fully understood,whereas some of which need more investigation.Increasing studies have indicated that cell death and cell autophagy caused by coronavirus might play an important role in virus infection and pathogenicity.However,the knowledge of the interactions and related mechanisms of SARS-CoV-2 between cell death and cell autophagy lacks systematic elucidation.Therefore,in this review,we comprehensively delineate how SARS-CoV-2 manipulates diverse cell death(including apoptosis,necroptosis,pyroptosis,ferroptosis,and NETosis)and cell autophagy for itself benefits,which is simultaneously involved in the occurrence and progression of COVID-19,aiming to provide a reasonable basis for the existing interventions and further development of novel therapies.Xue Li Ziqi Zhang Zhenling Wang Pedro Gutiérrez-Castrellón Huashan Shi 2022Signal Transduction and Targeted Therapy2022,7,7:1
7新型冠状病毒ORF3a蛋白质的生物信息学分析显示文摘目的用生物信息学分析严重急性呼吸综合征冠状病毒2(SARS-CoV-2)基因ORF3a蛋白质。方法从UniProt数据库获取ORF3a蛋白质的氨基酸序列,应用ProtParam tool分析其理化性质,SOPMA、SWISS-MODEL预测二、三级结构,PortScale、Signal IP 4.0 Server、TMHMM Server 2.0分析ORF3a蛋白质亲疏水性、信号肽、跨膜区。应用ABCpred、SYFPEITHI和NetPhos 3.1 Server预测B、T细胞表面抗原表位及磷酸化位点,VaxiJenv 2.0、AlgPred server预测抗原性和过敏原性。结果ORF3a蛋白质含275个氨基酸,为稳定、疏水性蛋白质,有3个跨膜螺旋区、29个磷酸化位点,含多个T、B细胞抗原表位,具有抗原性和非过敏原性。结论ORF3a蛋白质结构稳定,含多个T、B细胞抗原表位,可为研究SARS-CoV-2多表位疫苗提供基础。王瑄 李祥芳 丁寿鹏 吴利先 2023中国感染控制杂志2023,22,2:1
8柯萨奇病毒A16型3C蛋白对人横纹肌肉瘤细胞凋亡的诱导作用及其机制显示文摘目的:探讨柯萨奇病毒A16型(CA16)3C蛋白对横纹肌肉瘤RD细胞凋亡的影响,并阐明其可能的作用机制。方法:体外培养RD细胞,分为对照组(转染0.4µg空载体质粒pCMV-HA)、0.1μg pCMV-HA-3C组(转染0.1μg pCMV-HA-3C和0.3μg pCMV-HA)、0.2μg pCMV-HA-3C组(转染0.2μg pCMV-HA-3C和0.2μg pCMV-HA)、0.4μg pCMV-HA-3C组(转染0.4μg pCMV-HA-3C)和蛋白激酶B(AKT)激活剂SC79处理组(先用4 mg·L^(-1)SC79处理细胞4 h,然后转染0.2µg pCMV-HA-3C和0.2μg pCMV-HA)。MTT法检测各组细胞存活率,流式细胞术检测各组细胞凋亡率,实时荧光定量PCR(RT-qPCR)法检测各组RD细胞中Bcl-2同源拮抗剂/杀伤剂(Bak)、Bcl-2相关的细胞死亡激动剂(Bad)和p53上调凋亡调节因子(PUMA)mRNA表达水平,Western blotting法检测各组RD细胞中Bad、Bak、PUMA、聚ADP核糖聚合酶(PARP)、裂解聚ADP核糖聚合酶(cleaved-PARP)、裂解含半胱氨酸的天冬氨酸蛋白水解酶3(cleaved-caspase-3)、AKT和磷酸化AKT(p-AKT)蛋白表达水平。结果:与对照组比较,0.4µg pCMV-HA-3C组细胞存活率明显降低(P<0.01)。与对照组比较,不同剂量pCMV-HA-3C组细胞凋亡率明显升高(P<0.01)。与对照组比较,0.2µg pCMV-HA-3C组细胞中Bak、Bad和PUMA mRNA和蛋白表达水平均明显升高(P<0.05或P<0.01)。与对照组比较,不同剂量pCMV-HA-3C组细胞中cleaved-PARP和cleaved-caspase-3蛋白表达水平明显升高(P<0.05或P<0.01)。SC79处理实验中,与对照组比较,0.2μg pCMV-HA-3组细胞中cleaved-PARP、cleaved-caspase-3和AKT蛋白表达水平明显升高(P<0.05),p-AKT蛋白表达水平明显降低(P<0.01);与0.2μg pCMV-HA-3C组比较,SC79处理组细胞中cleaved-PARP、cleaved-caspase-3和AKT蛋白表达水平明显降低(P<0.05或P<0.01),p-AKT蛋白表达水平明显升高(P<0.01)。结论:CA16型3C蛋白可能通过抑制AKT信号通路诱导RD细胞凋亡。史颖颖 陈仕同 胡波 沈铎 朱旷 叶思玮 冯金梅 2021吉林大学学报(医学版)2021,47,4:0
9SARS-CoV-2辅助蛋白ORF6研究进展显示文摘2019年底新型冠状病毒(severe acute respirato-ry syndrome coronavirus 2,SARS-CoV-2)被发现后,在世界各地迅速传播,并迅速发展为席卷全球的重大公共卫生事件。在此之前,也曾有两种冠状病毒引起的感染引发全球关注,分别是2002年底出现的严重急性呼吸综合征冠状病毒(severe acute re-spiratory syndrome coronavirus,SARS-CoV)引起的非典型肺炎(severe acute respiratory syndrome,SARS)和2012年出现的中东呼吸综合征冠状病毒(middleeast respiratory syndrome coronavirus,MERS-CoV)引起的中东呼吸综合征(middle east respiratory syn-drome,MERS)。饶晶晶 曾凤 黄艳萍 付亚男 刘龙 杨靖 刘志新 2022湖北医药学院学报2022,41,4:0
10The glycosylation in SARS-CoV-2 and its receptor ACE2显示文摘Coronavirus disease 2019(COVID-19),a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected more than 235 million individuals and led to more than 4.8 million deaths worldwide as of October 52021.Cryo-electron microscopy and topology show that the SARS-CoV-2 genome encodes lots of highly glycosylated proteins,such as spike(S),envelope(E),membrane(M),and ORF3a proteins,which are responsible for host recognition,penetration,binding,recycling and pathogenesis.Here we reviewed the detections,substrates,biological functions of the glycosylation in SARS-CoV-2 proteins as well as the human receptor ACE2,and also summarized the approved and undergoing SARS-CoV-2 therapeutics associated with glycosylation.This review may not only broad the understanding of viral glycobiology,but also provide key clues for the development of new preventive and therapeutic methodologies against SARS-CoV-2 and its variants.Yanqiu Gong Suideng Qin Lunzhi Dai Zhixin Tian 2021Signal Transduction and Targeted Therapy2021,6,12:0
11Reducing SARS-CoV-2 pathological protein activity with small molecules显示文摘Coronaviruses are dangerous human and animal pathogens.The newly identified coronavirus SARS-CoV-2 is the causative agent of COVID-19 outbreak,which is a real threat to human health and life.The world has been struggling with this epidemic for about a year,yet there are still no targeted drugs and effective treatments are very limited.Due to the long process of developing new drugs,reposition of existing ones is one of the best ways to deal with an epidemic of emergency infectious diseases.Among the existing drugs,there are candidates potentially able to inhibit the SARS-CoV-2 replication,and thus inhibit the infection of the virus.Some therapeutics target several proteins,and many diseases share molecular paths.In such cases,the use of existing pharmaceuticals for more than one purpose can reduce the time needed to design new drugs.The aim of this review was to analyze the key targets of viral infection and potential drugs acting on them,as well as to discuss various strategies and therapeutic approaches,including the possible use of natural products.We highlighted the approach based on increasing the involvement of human deaminases,particularly APOBEC deaminases in editing of SARS-CoV-2 RNA.This can reduce the cytosine content in the viral genome,leading to the loss of its integrity.We also indicated the nucleic acid technologies as potential approaches for COVID-19 treatment.Among numerous promising natural products,we pointed out curcumin and cannabidiol as good candidates for being antiSARS-CoV-2 agents.Donata Pluskota-Karwatka Marcin Hoffmann Jan Barciszewski 2021Journal of Pharmaceutical Analysis2021,11,4:0
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