Vassilaki Niki, Papadimitriou Konstantinos, Ioannidis Anastasios, Papandreou Nikos C, Milona Raphaela S, Iconomidou Vassiliki A, Chatzipanagiotou Stylianos
Laboratory of Molecular Virology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, 11521 Athens, Greece.
Laboratory of Food Quality Control and Hygiene, Department of Food Science and Human Nutrition, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece.
Microorganisms. 2022 Jul 15;10(7):1430. doi: 10.3390/microorganisms10071430.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that belongs to the family, emerged in December 2019, causing the COVID-19 pandemic in March 2020. Unlike previous SARS and Middle East respiratory syndrome (MERS) outbreaks, this virus has a higher transmissibility rate, albeit a lower case fatality rate, which results in accumulation of a significant number of mutations and a faster evolution rate. Genomic studies on the mutation rate of the virus, as well as the identification of mutations that prevail and their impact on disease severity, are of great importance for pandemic surveillance and vaccine and drug development. Here, we aim to identify mutations on the SARS-CoV-2 viral genome and their effect on the proteins they are located in, in Greek patients infected in the first wave of the pandemic. To this end, we perform SARS-CoV-2 amplicon-based NGS sequencing on nasopharyngeal swab samples from Greek patients and bioinformatic analysis of the results. Although SARS-CoV-2 is considered genetically stable, we discover a variety of mutations on the viral genome. In detail, 18 mutations are detected in total on 10 SARS-CoV-2 isolates. The mutations are located on ORF1ab, S protein, M protein, ORF3a and ORF7a. Sixteen are also detected in patients from other regions around the world, and two are identified for the first time in the present study. Most of them result in amino acid substitutions. These substitutions are analyzed using computational tools, and the results indicate minor or major impact on the proteins' structural stability, which could probably affect viral transmissibility and pathogenesis. The correlation of these variations with the viral load levels is examined, and their implication for disease severity and the biology of the virus are discussed.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种属于该病毒家族的新型病毒，于2019年12月出现，在2020年3月引发了COVID-19大流行。与之前的SARS和中东呼吸综合征（MERS）疫情不同，这种病毒具有更高的传播率，尽管病死率较低，这导致了大量突变的积累和更快的进化速度。对该病毒突变率的基因组研究，以及对流行突变及其对疾病严重程度影响的鉴定，对于大流行监测以及疫苗和药物开发至关重要。在此，我们旨在识别希腊在大流行第一波中感染的患者体内SARS-CoV-2病毒基因组上的突变及其对所在蛋白质的影响。为此，我们对希腊患者的鼻咽拭子样本进行了基于SARS-CoV-2扩增子的NGS测序，并对结果进行生物信息学分析。尽管SARS-CoV-2被认为基因稳定，但我们在病毒基因组上发现了多种突变。具体而言，在10株SARS-CoV-2分离株中总共检测到18个突变。这些突变位于ORF1ab、S蛋白、M蛋白、ORF3a和ORF7a上。其中16个也在世界其他地区的患者中检测到，两个是本研究首次鉴定出的。它们大多数导致氨基酸替换。使用计算工具对这些替换进行分析，结果表明对蛋白质结构稳定性有轻微或重大影响，这可能会影响病毒的传播性和致病性。我们研究了这些变异与病毒载量水平的相关性，并讨论了它们对疾病严重程度和病毒生物学的影响。
