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Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.

新兴的SARS-CoV-2 突变热点包括一种新的RNA依赖-RNA聚合酶变体。

  • 影响因子:4.1240
  • DOI:10.1186/s12967-020-02344-6
  • 作者列表:"Pachetti M","Marini B","Benedetti F","Giudici F","Mauro E","Storici P","Masciovecchio C","Angeletti S","Ciccozzi M","Gallo RC","Zella D","Ippodrino R
  • 发表时间:2020-04-22

BACKGROUND:SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS:We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS:We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). CONCLUSIONS:These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.


背景: SARS-CoV-2 是一种负责严重急性呼吸综合征 (新型冠状病毒肺炎) 大流行的RNA冠状病毒。RNA病毒的特点是高突变率,高达其宿主的百万倍。病毒致突变能力取决于几个因素,包括复制核酸的病毒酶的保真度,如SARS-CoV-2 RNA依赖性RNA聚合酶 (RdRp)。突变率驱动病毒进化和基因组变异,从而使病毒逃避宿主免疫并产生耐药性。 方法: 我们分析了来自GISAID数据库的 220 个基因组序列,这些序列来源于 2019 年 12 月至 2020 年 3 月中旬全球感染SARS-CoV-2 的患者。从GenBank数据库获得SARS-CoV-2 参考基因组。使用Clustal Omega进行基因组比对。使用Mann-Whitney和Fisher精确检验评估统计学显著性。 结果: 我们鉴定了 8 个新的SARS-CoV-2 复发突变,位于 1397 、 2891 、 14408 、 17746 、 17857 、 18060 、 23403 和 28881 位。2891 、 3036 、 14408 、 23403 和 28881 位的突变主要在欧洲观察到,而位于 17746 、 17857 和 18060 位的突变仅在北美存在。我们于 2020 年 2 月 9 日在英国首次注意到RdRp基因的沉默突变,而 2 月 20 日出现了RdRp改变其氨基酸组成的不同突变,意大利 2020 年 (伦巴第)。RdRp突变的病毒中位数为 3 个点突变 [范围: 2-5],否则它们的中位数为 1 个突变 [范围: 0-3] (p值 <0。0 0 1)。 结论: 这些发现表明病毒正在进化,欧洲、北美和亚洲毒株可能共存,它们各自具有不同的突变模式。需要研究突变的RdRp对这种现象的贡献。迄今为止,几种针对RdRp酶的药物正在被用于SARS-CoV-2 感染治疗。其中一些在SARS-CoV-2 的RdRp疏水裂隙中具有预测的结合部分,与我们确定的 14408 突变相邻。因此,研究和鉴定SARS-CoV-2 RdRp突变以评估可能的耐药病毒表型非常重要。同样重要的是要认识到是否存在一些突变可能与不同的SARS-CoV-2 死亡率。



作者列表:["Lim J","Jeon S","Shin HY","Kim MJ","Seong YM","Lee WJ","Choe KW","Kang YM","Lee B","Park SJ"]

METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

作者列表:["Zhang W","Du RH","Li B","Zheng XS","Yang XL","Hu B","Wang YY","Xiao GF","Yan B","Shi ZL","Zhou P"]

METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

翻译标题与摘要 下载文献
作者列表:["Cheng ZJ","Shan J"]

METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.