Next-generation sequencing of Omicron SARS-CoV-2 variants in Hormozgan Province, Iran, and evaluation of the effects of mutations on RBD and ORF9b protein function

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution Pub Date : 2025-08-12 DOI:10.1016/j.meegid.2025.105812

Khadijeh Ahmadi , Soudabeh Kavousipour , Behzad Shahbazi , Farhad Farzin , Zahra Gharibi , Maryam Sadat Pishva , Ali Pishahang , Hamed Gouklani

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Abstract

The emergence of the Omicron variant in November 2021 marked a significant turning point in the COVID-19 pandemic due to its unprecedented number of mutations compared to previous variants. To better understand its clinical impact and evolutionary trajectory, we conducted a comprehensive genomic epidemiology study analyzing 528 SARS-CoV-2 samples collected in Iran between March 2021 and March 2023. Using nanopore sequencing with ≥96 % genome coverage and advanced bioinformatics tools including the Nextclade platform, we systematically characterized the mutational profiles of circulating variants with particular focus on the receptor-binding domain (RBD) and ORF9b proteins. Our analysis revealed BA.5.2 as the dominant strain (32.4 % prevalence), followed by XBB.1.9.1 (14.2 %), with only 17.6 % of cases occurring in vaccinated individuals. Through molecular docking and dynamics simulations, we demonstrated that key variants including BA.5.2, XBB.1.5, and XBB.1.9 exhibit enhanced binding affinity to host receptors, with RBD showing stronger interactions with ACE2 and ORF9b variants displaying improved binding to TOM70. Notably, our findings suggest similar pathogenic potential between the XBB.1.5/XBB.1.9 and BA.5 lineages, while highlighting the utility of whole genome entropy analysis for predicting viral evolution patterns. These results provide valuable insights for guiding vaccine development, therapeutic design, and public health strategies against evolving SARS-CoV-2 variants.

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伊朗霍尔木兹甘省SARS-CoV-2 Omicron变异的新一代测序及突变对RBD和ORF9b蛋白功能的影响

与之前的变异相比，欧米克隆变异在2021年11月的出现标志着COVID-19大流行的一个重要转折点，因为它的突变数量前所未有。为了更好地了解其临床影响和进化轨迹，我们对2021年3月至2023年3月在伊朗收集的528份SARS-CoV-2样本进行了全面的基因组流行病学研究。利用基因组覆盖率≥96%的纳米孔测序和先进的生物信息学工具（包括Nextclade平台），我们系统地表征了循环变异的突变谱，特别关注受体结合域（RBD）和ORF9b蛋白。我们的分析显示BA.5.2为优势菌株（32.4%），其次是XBB.1.9.1(14.2%)，仅17.6%的病例发生在接种疫苗的个体中。通过分子对接和动力学模拟，我们发现BA.5.2、XBB.1.5和XBB.1.9等关键变异体与宿主受体的结合亲和力增强，其中RBD与ACE2的相互作用更强，ORF9b变异体与TOM70的结合能力增强。值得注意的是，我们的研究结果表明XBB.1.5/XBB.1.9和BA.5谱系之间具有相似的致病潜力，同时强调了全基因组熵分析在预测病毒进化模式方面的实用性。这些结果为指导疫苗开发、治疗设计和针对不断演变的SARS-CoV-2变体的公共卫生策略提供了有价值的见解。

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来源期刊

Infection Genetics and Evolution 医学-传染病学

CiteScore

8.40

自引率

0.00%

发文量

215

审稿时长

82 days

期刊介绍： (aka Journal of Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases -- MEEGID) Infectious diseases constitute one of the main challenges to medical science in the coming century. The impressive development of molecular megatechnologies and of bioinformatics have greatly increased our knowledge of the evolution, transmission and pathogenicity of infectious diseases. Research has shown that host susceptibility to many infectious diseases has a genetic basis. Furthermore, much is now known on the molecular epidemiology, evolution and virulence of pathogenic agents, as well as their resistance to drugs, vaccines, and antibiotics. Equally, research on the genetics of disease vectors has greatly improved our understanding of their systematics, has increased our capacity to identify target populations for control or intervention, and has provided detailed information on the mechanisms of insecticide resistance. However, the genetics and evolutionary biology of hosts, pathogens and vectors have tended to develop as three separate fields of research. This artificial compartmentalisation is of concern due to our growing appreciation of the strong co-evolutionary interactions among hosts, pathogens and vectors. Infection, Genetics and Evolution and its companion congress [MEEGID](http://www.meegidconference.com/) (for Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases) are the main forum acting for the cross-fertilization between evolutionary science and biomedical research on infectious diseases. Infection, Genetics and Evolution is the only journal that welcomes articles dealing with the genetics and evolutionary biology of hosts, pathogens and vectors, and coevolution processes among them in relation to infection and disease manifestation. All infectious models enter the scope of the journal, including pathogens of humans, animals and plants, either parasites, fungi, bacteria, viruses or prions. The journal welcomes articles dealing with genetics, population genetics, genomics, postgenomics, gene expression, evolutionary biology, population dynamics, mathematical modeling and bioinformatics. We also provide many author benefits, such as free PDFs, a liberal copyright policy, special discounts on Elsevier publications and much more. Please click here for more information on our author services .