Implications of the Novel Mutations in the SARS-CoV-2 Genome for Transmission, Disease Severity, and the Vaccine Development.
Implications of the Novel Mutations in the SARS-CoV-2 Genome for Transmission, Disease Severity, and the Vaccine Development.
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SARS-CoV-2 基因组新突变对传播、疾病严重程度和疫苗开发的影响。
DOI：
10.3389/fmed.2021.636532
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发表时间：
2021
影响因子：
3.9
通讯作者：
Akkiz H
中科院分区：
文献类型：
--
作者：
Akkiz H
2019年12月下旬，中国发现了2019冠状病毒病（COVID-19）的致病病毒--严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）。SARS-CoV-2是冠状病毒科（Coronaviridae）的一种有包膜、正义、单链RNA β冠状病毒。冠状病毒具有纠正复制错误的遗传校正机制，因此SARS-CoV-2的遗传多样性极低。尽管该病毒的突变率较低，但研究人员在SARS-CoV-2基因组中共检测到12，706个突变，其中大多数是单核苷酸多态性。测序数据显示，SARS-CoV-2在其基因组中每月积累两个单核苷酸突变。最近，由于原始参考基因型中刺突蛋白第614个氨基酸位置的第23，403位腺嘌呤至鸟嘌呤核苷酸变化，确定了氨基酸天冬氨酸（D）至甘氨酸（G）（D 614 G）突变。携带刺突蛋白D 614 G突变的SARS-CoV-2病毒已成为世界范围内的优势变异株。已发现D 614 G突变与刺突蛋白中的其他3个突变相关。临床和假病毒实验研究表明，刺突蛋白D 614 G突变改变了病毒表型。然而，突变对人与人之间传播率、疾病严重程度以及疫苗和治疗开发的影响仍不清楚。最近发现了SARS-CoV-2的三种变体。它们是B.1.1.7（英国）变体、B.1.351（N501Y.V2，南非）变体和B.1.1.28（巴西）变体。流行病学数据表明，它们比原始变体具有更高的传播性。有报道称，一些疫苗对B.1.351变体的有效性较低。本文综述了SARS-CoV-2基因组中新突变对传播、临床结果和疫苗开发的影响。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 (COVID-19), has been identified in China in late December 2019. SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the Coronaviridae family. Coronaviruses have genetic proofreading mechanism that corrects copying mistakes and thus SARS-CoV-2 genetic diversity is extremely low. Despite lower mutation rate of the virus, researchers have detected a total of 12,706 mutations in the SARS-CoV-2 genome, the majority of which were single nucleotide polymorphisms. Sequencing data revealed that the SARS-CoV-2 accumulates two-single nucleotide mutations per month in its genome. Recently, an amino acid aspartate (D) to glycine (G) (D614G) mutation due to an adenine to guanine nucleotide change at position 23,403 at the 614th amino-acid position of the spike protein in the original reference genotype has been identified. The SARS-CoV-2 viruses that carry the spike protein D614G mutation have become dominant variant around the world. The D614G mutation has been found to be associated with 3 other mutations in the spike protein. Clinical and pseudovirus experimental studies have demonstrated that the spike protein D614G mutation alters the virus phenotype. However, the impact of the mutation on the rate of transmission between people, disease severity and the vaccine and therapeutic development remains unclear. Three variants of SARS-CoV-2 have recently been identified. They are B.1.1.7 (UK) variant, B.1.351 (N501Y.V2, South African) variant and B.1.1.28 (Brazilian) variant. Epidemiological data suggest that they have a higher transmissibility than the original variant. There are reports that some vaccines are less efficacious against the B.1.351 variant. This review article discusses the effects of novel mutations in the SARS-CoV-2 genome on transmission, clinical outcomes and vaccine development.