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[传染病] 新型冠状病毒(2019-nCoV)

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发表于 2020-1-30 00:02:14 | 显示全部楼层 |阅读模式
2019年新型冠状病毒(2019-nCoV)[3] [4]也被称为武汉冠状病毒,[1]是一种传染性病毒,可引起呼吸感染,并已显示出人与人之间的传播,这是相关首先发现的证据 在中国湖北武汉市,是造成2019-20年度武汉冠状病毒爆发的原因。[5] 基因组测序表明,它是一种正义的单链RNA冠状病毒。[6] [7] [8]

据报道,最初的病例与大型海鲜和动物市场有流行病学联系,尽管没有得到证实,但该病毒被认为是人畜共患病起源。[9] 比较该病毒与其他现有病毒样品的基因序列,已显示出与SARS-CoV(79.5%)[10]和蝙蝠冠状病毒(96%)[10]相似,[10]可能起源于蝙蝠。[11] [ 12] [13]


两种2019-nCoV病毒体的透射电子显微照片

内容
1 流行病学
2 治疗
3 病毒学
3.1 感染
3.2 蓄水池
3.3 系统发生学和分类学
3.4 结构生物学
4 疫苗研究
5 参考

流行病学
主要文章:2019–20武汉冠状病毒爆发
首次已知的人类感染发生在2019年12月上旬。分子钟方法显示了相似的或稍早的起源日期。[14]

2019年12月中旬,在中国武汉首次发现了2019-nCoV暴发。该病毒随后传播到了中国大陆的其他省和其他国家,包括泰国,日本,台湾,韩国,澳大利亚,法国和 美国。[15] [16] [17]

截至2020年1月28日(世界标准时间08:00),确诊病例为4,474例,其中4,409例在中国大陆内。[18]迄今为止,在中国境外的案例是曾从武汉旅行或与从该地区旅行的人直接接触的人。[19]截至2020年1月28日,死亡人数为107。[18] 2020年1月20日在中国广东省确认了人与人之间的传播。[20]

治疗
目前尚无特定的治疗方法,因此治疗的重点是减轻症状,[21]在严重的情况下,包括发烧,疲劳,干咳和呼吸急促,或肺炎和肾衰竭。[22] [23] [24 ]中国疾病预防控制中心(CCDC)正在测试现有的肺炎治疗方法,以治疗冠状病毒相关的肺炎。[25]

现有的抗病毒药物正在研究中[21],包括蛋白酶抑制剂,如茚地那韦,沙奎那韦,瑞姆昔韦,洛匹那韦/利托那韦和干扰素β。[26] [27]先前鉴定出的单克隆抗体(mAbs)的有效性也在研究之中。[28]

病毒学
感染
该病毒已在人与人之间传播。[20]有报道说,即使在潜伏期,该病毒也具有传染性。[29] [30]截至2020年1月27日,美国疾病控制与预防中心(CDC)的官员表示,“他们没有任何证据表明患者在症状发作之前具有传染性。” [31] [32]

一个研究小组估计,该病毒的基本繁殖数({\ displaystyle R_ {0}} R_ {0},发音为R-nought)在3到5之间,[33]这意味着该病毒通常每人感染3到5个人确定的感染。其他研究小组估计基本繁殖数量在1.4至3.8之间。[34]已经确定该病毒能够沿至少四个人的链传播。[35]

蓄水池
在2019-20爆发之前,《自然医学》(Nature Medicine)上发表的2015年研究警告说,中国蝙蝠种群中传播的病毒可能会再次出现SARS-CoV的潜在风险。使用SARS-CoV逆向遗传系统,拉尔夫·巴里奇(Ralph Baric)的团队生成并鉴定了一种嵌合病毒,该病毒在适应小鼠的SARS-CoV主链中表达蝙蝠冠状病毒SHC014的尖峰。单克隆SARS抗体和SARS疫苗均无法使用新型刺突蛋白中和并不能被这种CoV感染。[36] [需要澄清]

出售食物的动物被怀疑是蓄水池或中间人,因为最早发现的许多感染者是华南海鲜市场的工人。因此,它们更容易与动物接触。[37] 2003年的非典疫情也归咎于以动物为食的市场。这样的市场被认为是新型病原体的理想孵化器。[38]

利用足够数量的测序基因组,可以重建病毒家族突变史的系统树。在对SARS 2003流行病的起源进行的17年研究中,分离并测序了许多SARS样蝙蝠冠状病毒,其中大多数来源于蝙蝠的Rhinolophus蝙蝠属。已经发现武汉新型冠状病毒属于SARS相关冠状病毒的这一类别。 2015年和2017年发表的两条中华犀牛基因组序列与2019-nCoV相似,为80%。[11] [12]据说,来自犀牛亲缘关系的第三个未发表的病毒基因组“ RaTG13”与2019-nCoV有96%的相似性。[39]为了进行比较,这种病毒之间的变异量类似于在H3N2人类流感病毒株中十年来观察到的突变量。[40]

疫情的爆发和可能的来源迫使中国在疫情爆发之时禁止野生动植物贸易和消费。[41]专家仍对未来发出警告:“如果这些市场持续存在,并且人类对非法和不受管制的野生动植物的消费继续存在,那么公众将继续面临新出现的新病毒带来的更大风险,这可能会带来更大的致命性和未来大流行的蔓延。” 。“这些是为这些病毒的出现创造机会的理想实验室。” [41]

系统发育学和分类学
基因组信息


2019-nCoV属于被称为冠状病毒的广泛病毒家族。其他冠状病毒能够引起多种疾病,从普通感冒到更严重的疾病,例如中东呼吸综合症(MERS)和严重急性呼吸综合症(SARS)。这是继229E,NL63,OC43,HKU1,MERS-CoV和SARS-CoV之后的第七种感染人的冠状病毒。[42]

尽管在遗传上不同于感染人类的****其他冠状病毒,但它与SARS-COV一样,是Sarbecovirus亚型(β-CoV谱系B)的成员。[43] [37] [44]它的RNA序列长约30 kb。[8]

到1月12日,新的冠状病毒基因组已从武汉分离出,并由中国疾病预防控制中心及其他机构报告; [8] [45] [46]到1月26日,基因组数目已增至28个。除了最早的GenBank基因组,这些基因组都在GISAID禁运下。可通过Nextstrain对样品进行系统发育分析。[47]

结构生物学


2019-nCoV蛋白酶的Innophore Phyre2带状图,抗病毒药物的潜在靶点[48]
基因组的出版物导致对nCoV尖峰(S)蛋白的受体结合蛋白(RBD)进行了几次蛋白质建模实验,表明S蛋白与血管紧张素转化酶2(ACE2)受体保持足够的亲和力,可将其用作受体。细胞进入的机制。[49] 1月22日,中国的一个研究完整病毒的研究小组和美国的一个研究逆向遗传学的研究小组独立并通过实验证明了ACE2作为2019-nCoV的受体。[50] [51] [52]

为了寻找潜在的蛋白酶抑制剂,还对来自Orf1a多蛋白的病毒3C样蛋白酶M(pro)进行了药物对接实验的建模。 Innophore已经产生了两个基于SARS蛋白酶的计算模型,[48]而中国科学院已经产生了未发表的重组2019-nCoV蛋白酶的实验结构。[53]

疫苗研究
到2020年1月,一些组织和机构开始根据已发表的基因组为武汉冠状病毒创建疫苗。[54] [55]

在中国,中国疾病预防控制中心正在开发一种针对新型冠状病毒的疫苗。[25] [56]

流行病防范创新联盟(CEPI)支持了三个疫苗项目,其中一个项目由生物技术公司Moderna进行,另一个项目由昆士兰大学进行。[57]美国国立卫生研究院(NIH)正在与Moderna合作生产与冠状病毒表面刺突相匹配的RNA疫苗,并希望在2020年5月之前开始生产。[54]在澳大利亚,昆士兰大学正在研究一种分子钳疫苗的潜力,该疫苗可以对病毒蛋白进行基因修饰,使其模仿冠状病毒并刺激免疫反应。[57]

在一个独立的项目中,加拿大公共卫生局已批准萨斯喀彻温大学疫苗和传染病组织-国际疫苗中心(VIDO-InterVac)着手开发疫苗。[58] VIDO-InterVac旨在于2020年3月开始生产和动物测试,并于2021年开始进行人体测试。[55]

据网上相关报道,香港大学的袁国勇研究员和他的研究小组曾在2003年爆发SARS冠状病毒期间参加过研究,他们宣布那里正在开发疫苗,但尚未进行动物试验。[59]

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