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Making sense of spike d614g in SARS-CoV-2 transmission

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Science China(Life Sciences) 2021年第7期64卷 1062-1067页

作者： Aria C.Shi Xuping Xie School of Medicine Johns Hopkins UniversityBaltimoreMD 21205USA department of Biochemistry and Molecular Biology University of Texas Medical BranchGalvestonTX 77550USA

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiologic agent of the current coronavirus disease 2019(COVId-19)pandemic,has evolved to adapt to human host and transmission over the past 12 *** prominent adaptive mutation is the asparagine-to-glycine substitution at amino acid position 614 in the viral spike protein(d614g),which has become dominant in the currently circulating virus *** spike protein determines host ranges,tissue tropism,and pathogenesis through binding to the cellular receptor of angiotensin converting enzyme 2(ACE2),the d614g mutation is hypothesized to enhance viral fitness in human host,leading to increased transmission during the global *** we summarize the recent progress on the role of the d614g mutation in viral replication,pathogenesis,transmission,and vaccine and therapeutic antibody *** findings underscore the importance in closely monitoring viral evolution and defining their functions to ensure countermeasure efficacy against newly emerging variants.

关键词： SARS-CoV-2 d614g COVId-19

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d614g突变对新型冠状病毒致病性、免疫原性的影响

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生物技术 2022年第3期32卷 366-372,349页

作者：卫紫钰邵金辉湖北文理学院基础医学院人体解剖与组织学胚胎学教研室湖北襄阳441053

新型冠状病毒(SARS-CoV-2)d614g突变体的棘突蛋白中614位氨基酸的天冬酰胺(d)被甘氨酸(g)取代,这在目前流行的病毒株中已占优势。该文综述2021年以来所发表的与d614g突变密切相关文献,内容涉及d614g突变对棘突蛋白结构的影响,d614g突变... 详细信息

新型冠状病毒(SARS-CoV-2)d614g突变体的棘突蛋白中614位氨基酸的天冬酰胺(d)被甘氨酸(g)取代,这在目前流行的病毒株中已占优势。该文综述2021年以来所发表的与d614g突变密切相关文献,内容涉及d614g突变对棘突蛋白结构的影响,d614g突变对新冠病毒致病性的影响,d614g突变与新冠病毒免疫原性及其疫苗的关系,d614g突变在一些国家新冠病毒中的情况,含d614g突变体新冠病毒的诊断与治疗等,以及对这些研究结果的初步分析。将有助于对含d614g突变新型冠状病毒疫情的深入了解与防控。

关键词：新型冠状病毒 d614g 棘突蛋白突变疫苗

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d614g突变是否会使新冠病毒更危险 003

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The twin-beginnings of COVId-19 in Asia and Europe—one prevails quickly

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作者：冯玉婧

新冠疫情在全球蔓延之际，马来西亚卫生部总监努尔·希沙姆日前在社交媒体上发文说，该国最近从分属两起聚集性感染的4名患者体内分离到携带d614g突变的新冠病毒毒株，并称发生这一突变的毒株“具有10倍的传染性”。对于变异毒株传播范... 详细信息

新冠疫情在全球蔓延之际，马来西亚卫生部总监努尔·希沙姆日前在社交媒体上发文说，该国最近从分属两起聚集性感染的4名患者体内分离到携带d614g突变的新冠病毒毒株，并称发生这一突变的毒株“具有10倍的传染性”。对于变异毒株传播范围的扩大，公众担忧的是，携带这种名?

关键词：刺突蛋白 d614g

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National Science Review 2022年第4期9卷 51-59页

作者： Yongsen Ruan Haijun Wen Mei Hou Ziwen He Xuemei Lu Yongbiao Xue Xionglei He Ya-Ping Zhang Chung-I Wu State Key Laboratory of Biocontrol School of Life SciencesSouthern Marine Science and Engineering Guangdong Laboratory (Zhuhai)Sun Yat-sen University department of Ecology and Evolution University of Chicago State Key Laboratory of genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences Beijing Institute of genomics Chinese Academy of Sciencesand China National Centre for Bioinformation

In the spread of SARS-C oV-2,there have been multiple waves of replacement between strains,each of which having a distinct set of *** first wave is a group of four mutations(C241 T,C3037 T,C14408 T and A23403 g [this being the amino acid change d614 g];all designated 0 to 1 below).This dg(d614 g) group,fixed at the start of the pandemic,is the foundation of all subsequent waves of ***,the dg group is absent in early Asian samples but present(and likely common) in Europe from the *** data show that the high fitness of dg1111 requires the synergistic effect of all four ***,the European strains would have had no time to evolve the four dg mutations(0 to1),had they come directly from the early Asian dg0000 *** likely,the European dg1111 strain had acquired the highly adaptive dg mutations in pre-pandemic Europe and had been spreading in parallel with the Asian *** recent reports further support this twin-beginning *** was a period of two-way spread between Asia and Europe but,by May 2020,the European strains had supplanted the Asian strains *** large-scale replacement of one set of mutations for another has since been replayed many times as COVId-19 progresses.

关键词： SARS-CoV-2 COVId-19 d614g twin-beginnings fitness advantage

天津滨海新区本土疫情新型冠状病毒全基因组测序和溯源分析

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中华微生物学和免疫学杂志 2021年第8期41卷 581-587页

作者：郑宝璐高鑫庄志超苏承邹明于爱萍谭昭麟李晓燕天津市疾病预防控制中心病原生物检测室 300011 天津市疾病预防控制中心传染病预防控制室 300011

目的对引起天津滨海新区本土新型冠状病毒肺炎(COVId-19,简称新冠肺炎)疫情的新型冠状病毒(SARS-CoV-2,简称新冠病毒)进行全基因组溯源及变异情况分析。方法对2020年11月7日至12月5日采集的天津滨海新区新冠肺炎疫情1例本地无症状感染者... 详细信息

目的对引起天津滨海新区本土新型冠状病毒肺炎(COVId-19,简称新冠肺炎)疫情的新型冠状病毒(SARS-CoV-2,简称新冠病毒)进行全基因组溯源及变异情况分析。方法对2020年11月7日至12月5日采集的天津滨海新区新冠肺炎疫情1例本地无症状感染者和5例确诊病例咽拭子样本进行全基因组高通量测序,de novo拼接测序数据,使用MAFFT v7.0多重序列比对程序和MEgA X软件对上述数据进行比对和构建系统进化树(Neighbor-joining法)。结果6株新冠病毒序列与武汉参考序列(Wuhan-Hu-1)基因相似度均大于99.9%;6株病毒中2株基因完全相同,符合L基因型欧洲家系分支Ⅱ.1(北美分支)/B.1特征;另外4株基因完全相同,符合L基因型欧洲家系分支Ⅰ/B.1.1特征,此6株新冠病毒序列分属不同的进化分支,为两条不同的传播链。6株新冠病毒序列共有18个核苷酸突变位点,其中8个位点是同义突变,9个位点为错义突变,产生9个氨基酸突变位点,均发现RdRp-P323L、S-d614g重要变异位点。结论本研究中天津滨海新区新冠肺炎疫情为两起事件,6株新冠病毒序列分属不同的进化分支,为两条不同的传播链。提示可能来源于搬运工人接触了已污染新冠病毒的不同来源进口冷链物品。6株新冠病毒序列均有P323L、d614g突变,病毒突变、传播能力更强,应持续加强天津冷链重点从业人员及本土、输入性病例的监测。

关键词：新型冠状病毒新型冠状病毒肺炎冷冻食品 P323L d614g

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Covid-19 Mutations and the Effect of different Vaccines on Immune Memory

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Journal of Endocrinology Research 2021年第1期3卷 32-40页

作者： Xanya Sofra City University LondonNew School for Social ResearchNew Yorkthe United States

We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and *** their close kinship,SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions,and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds.A single amino acid substitution such as replacing Aspartate(d)with glycine(g)composes the d614g mutation that is around 20%more infectious than its predecessor *** B117 variant,that exhibits a 70%transmissibility rate,harbours 23 mutants,each reflecting one amino acid *** examined several globally spreading mutations,501.V2,B1351,P1,and others,with respect to the specific amino acid conversions *** previous versions of coronavirus,where random mutations eventually precipitate extinction,the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious,facilitating its ability to evade detection,thus challenging the effectiveness of a large variety of emerging *** enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein,restricting the virus from releasing its contents into the *** antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I,compromising adaptive efficiency to recognize the virus,possibly provoking a cytokine storm that injures vital *** respect to that perspective,the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version,the Adenovirus dNA,Spike protein subunits,the deactivated virus genres,or,finally,the live attenuated coronavirus that a

关键词： SARS-CoV2 Covid-19 mRNA vaccines dNA vaccines Inactivated virus vaccines Covid-19 mutations d614g B117 P1 501Y.V2 Immune memory Spike protein

Vaccines’ Safety and Effectiveness in the Midst of Covid-19 Mutations

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Health 2021年第3期13卷 283-298页

作者： Xanya Sofra City University London UK New School for Social Research New York USA

We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus dNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the Cd8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.

关键词： SARS-CoV2 Covid-19 mRNA Vaccines dNA Vaccines Inactivated Virus Vaccines Covid-19 Mutations d614g B117 P1 501Y.V2 Immune Memory Spike Protein

氨基酸突变对S蛋白理化性质与SARS-CoV-2感染力影响的研究

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氨基酸突变对S蛋白理化性质与SARS-CoV-2感染力影响的研究

作者：杨子江北京交通大学

学位级别：硕士

目的:构建严重急性呼吸系统综合征冠状病毒2(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)不同突变体的突刺糖蛋白(Spike glycoprotein,S 蛋白)的三维结构,计算各突变体S蛋白与ACE2亲和力、三聚体稳定性、单体稳定性... 详细信息

目的:构建严重急性呼吸系统综合征冠状病毒2(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)不同突变体的突刺糖蛋白(Spike glycoprotein,S 蛋白)的三维结构,计算各突变体S蛋白与ACE2亲和力、三聚体稳定性、单体稳定性、三聚体间亲和力以及S1与S2亚基间的稳定性五项能量参数,研究d614g氨基酸替换突变对S蛋白理化性质的影响,探寻d614g突变增强SARS-CoV-2在人类细胞间感染力的机制,同时探寻这五项能量参数与SARS-CoV-2感染力的相关关系。希望建立一条仅需要S蛋白氨基酸序列,以S蛋白能量参数为依据,即可对SARS-CoV-2突变株进行感染力预测的途径,为公共卫生与流行病防控工作提供预警与建议。方法:首先根据选取的67个突变体,修改S蛋白氨基酸序列,使用SwissModel软件进行S蛋白三维结构建模,获得各突变体S蛋白三维结构。然后采用蛋白质能量计算软件FoldX,计算突变体S蛋白的五项能量参数。我们将d614g突变体的五项参数与参考株系野生型病毒Wuhan-1以及其他突变体进行对比统计分析,确定d614g对S蛋白这五项能量参数的影响,从而探寻d614g突变增强SARS-CoV-2在人类细胞间感染力的机制。同时通过相关性检验与回归分析等统计方法,探寻这五项能量参数对SARS-CoV-2感染力的影响。结果:我们发现d614g突变体S蛋白相较于野生型病毒Wuhan-1与其他突变体S蛋白具有更强的三聚体稳定性、三聚体间亲和力以及S1与S2亚基之间的稳定性。而d614g突变体与野生型Wuhan-1及其他突变体的S蛋白ACE2间亲和力与单体稳定性这两项能量参数并没有显著的差异。同时发现d614g突变与其他位点突变同时发生时,对五项能量参数的影响不是线性相加关系,并且d614g会增强原突变体S蛋白的三聚体稳定性、三聚体间亲和力以及S1与S2亚基之间的稳定性,不会影响原有突变体S蛋白与ACE2之间的亲和力与单体稳定性。我们发现了 SARS-CoV-2突变体假病毒感染力与五项参数的相关关系。本文选取的突变体感染力与S蛋白三聚体稳定性呈正向相关性,三聚体折叠能每减少1kcal/mol,三聚体稳定性增强,病毒的感染力增强0.0049倍。感染力与三聚体间亲和力同样呈正向相关性,三聚体间结合能每减少1kcal/mol,三聚体间亲和力增强,病毒的感染力增强0.027倍。感染力与S蛋白S1与S2亚基之间的稳定性也呈正向相关性,亚基间结合能每减少1kcal/mol,S1-S2亚基间稳定性增强,病毒的感染力增强0.549倍。由于本文选取的所有突变体S蛋白与ACE2间亲和力以及单体稳定性,与感染力之间并没有显著的相关关系,本研究无法判断SARS-CoV-2的感染力与这两项能量参数的相关关系。结论:d614g突变对S蛋白能量参数的影响:1)d614g突变相较于其他位点的突变并没有对S蛋白与ACE2之间亲和力与单体稳定性带来显著的影响;2)d614g突变相较于其他位点的突变显著增强了 S蛋白三聚体稳定性、三聚体间亲和力以及S1-S2亚基间稳定性;3)d614g突变与其他位点同时突变时,能量变化不是简单的线性相加,且d614突变同时发生会增强其他突变体的S蛋白三聚体稳定性、三聚体间亲和力以及S1-S2亚基间稳定性。S蛋白能量参数与SARS-CoV-2感染力的相关关系:1)本文选取的突变体感染力与S蛋白ACE2之间的亲和力以及单体稳定性不存在明显的相关关系,本研究无法确定感染力与这两项能量参数的相关关系;2)本文选取的突变体感染力与S蛋白三聚体稳定性、S蛋白三聚体间亲和力以及S蛋白S1-S2亚基间稳定性呈正相关关系;3)S蛋白三聚体稳定性与三聚体间亲和力高度相关,可以仅通过三聚体间亲和力与S1-S2亚基间稳定性进行SARS-CoV-2感染力预测。

关键词： SARS-CoV-2 氨基酸突变 d614g S蛋白三维结构能量参数 SARS-CoV-2 感染力