Center for Advanced Technologies, Tashkent, Uzbekistan.
Center of Genomics and Bioinformatics, Academy of Sciences of Uzbekistan, Qibray Region, Tashkent, Republic of Uzbekistan.
PLoS One. 2022 Jun 27;17(6):e0270314. doi: 10.1371/journal.pone.0270314. eCollection 2022.
Tracking temporal and spatial genomic changes and evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are among the most urgent research topics worldwide, which help to elucidate the coronavirus disease 2019 (COVID-19) pathogenesis and the effect of deleterious variants. Our current study concentrates genetic diversity of SARS-CoV-2 variants in Uzbekistan and their associations with COVID-19 severity. Thirty-nine whole genome sequences (WGS) of SARS-CoV-2 isolated from PCR-positive patients from Tashkent, Uzbekistan for the period of July-August 2021, were generated and further subjected to further genomic analysis. Genome-wide annotations of clinical isolates from our study have revealed a total of 223 nucleotide-level variations including SNPs and 34 deletions at different positions throughout the entire genome of SARS-CoV-2. These changes included two novel mutations at the Nonstructural protein (Nsp) 13: A85P and Nsp12: Y479N, which were unreported previously. There were two groups of co-occurred substitution patterns: the missense mutations in the Spike (S): D614G, Open Reading Frame (ORF) 1b: P314L, Nsp3: F924, 5`UTR:C241T; Nsp3:P2046L and Nsp3:P2287S, and the synonymous mutations in the Nsp4:D2907 (C8986T), Nsp6:T3646A and Nsp14:A1918V regions, respectively. The "Nextstrain" clustered the largest number of SARS-CoV-2 strains into the Delta clade (n = 32; 82%), followed by two Alpha-originated (n = 4; 10,3%) and 20A (n = 3; 7,7%) clades. Geographically the Delta clade sample sequences were grouped into several clusters with the SARS-CoV genotypes from Russia, Denmark, USA, Egypt and Bangladesh. Phylogenetically, the Delta isolates in our study belong to the two main subclades 21A (56%) and 21J (44%). We found that females were more affected by 21A, whereas males by 21J variant (χ2 = 4.57; p ≤ 0.05, n = 32). The amino acid substitution ORF7a:P45L in the Delta isolates found to be significantly associated with disease severity. In conclusion, this study evidenced that Identified novel substitutions Nsp13: A85P and Nsp12: Y479N, have a destabilizing effect, while missense substitution ORF7a: P45L significantly associated with disease severity.
追踪严重急性呼吸系统综合症冠状病毒 2 型（SARS-CoV-2）的时空基因组变化和演化是全球最紧迫的研究课题之一，有助于阐明 2019 年冠状病毒病（COVID-19）的发病机制和有害变异的影响。我们目前的研究集中在乌兹别克斯坦 SARS-CoV-2 变异的遗传多样性及其与 COVID-19 严重程度的关系。从 2021 年 7 月至 8 月在乌兹别克斯坦塔什干从 PCR 阳性患者中分离出的 39 株 SARS-CoV-2 全长基因组（WGS）序列，进一步进行了基因组分析。对本研究中临床分离株的全基因组注释显示，在整个 SARS-CoV-2 基因组的不同位置总共存在 223 个核苷酸水平的变异，包括 SNP 和 34 个缺失。这些变化包括非结构蛋白（Nsp）13 中的两个新突变：A85P 和 Nsp12：Y479N，这两个突变以前没有报道过。有两组同时发生的取代模式：刺突（S）中的错义突变：D614G、开放阅读框（ORF）1b：P314L、Nsp3：F924、5`UTR：C241T；Nsp3：P2046L 和 Nsp3：P2287S，以及 Nsp4：D2907（C8986T）、Nsp6：T3646A 和 Nsp14：A1918V 区域的同义突变。“Nextstrain”将最大数量的 SARS-CoV-2 株聚类到德尔塔分支（n = 32；82%），其次是两个源自阿尔法的（n = 4；10.3%）和 20A 分支（n = 3；7.7%）。从地理上看，德尔塔分支的样本序列被分成几个簇，与来自俄罗斯、丹麦、美国、埃及和孟加拉国的 SARS-CoV 基因型有关。系统发育上，本研究中的德尔塔分离株属于两个主要亚分支 21A（56%）和 21J（44%）。我们发现，21A 变异更易影响女性，而 21J 变异则更易影响男性（χ2 = 4.57；p ≤ 0.05，n = 32）。在德尔塔分离株中发现的 ORF7a：P45L 氨基酸取代与疾病严重程度显著相关。总之，本研究表明，鉴定出的新型取代 Nsp13：A85P 和 Nsp12：Y479N 具有不稳定作用，而错义取代 ORF7a：P45L 则与疾病严重程度显著相关。
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