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埃及新型冠状病毒肺炎冠状病毒2(SARS-CoV-2)的基因组特征:对刺突蛋白热力学稳定性的见解

Genomic characterization of SARS-CoV-2 in Egypt: insights into spike protein thermodynamic stability.

作者信息

Jalal Deena, Samir Omar, Elzayat Mariam G, El-Shqanqery Hend E, Diab Aya A, ElKaialy Lamiaa, Mohammed Aya M, Hamdy Donia, Matar Islam K, Amer Khaled, Elnakib Mostafa, Hassan Wael, Mansour Tarek, Soliman Sonia, Hassan Reem, Al-Toukhy Ghada M, Hammad Mahmoud, Abdo Ibrahim, Sayed Ahmed A

机构信息

Department of Basic Research, Genomics and Epigenomics Program, Children's Cancer Hospital Egypt 57357, Cairo, Egypt.

Department of Chemistry, Saint Mary's University, Halifax, NS, Canada.

出版信息

Front Microbiol. 2023 Jun 2;14:1190133. doi: 10.3389/fmicb.2023.1190133. eCollection 2023.

DOI:10.3389/fmicb.2023.1190133
PMID:37333655
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10273679/
Abstract

The overall pattern of the SARS-CoV-2 pandemic so far has been a series of waves; surges in new cases followed by declines. The appearance of novel mutations and variants underlie the rises in infections, making surveillance of SARS-CoV-2 mutations and prediction of variant evolution of utmost importance. In this study, we sequenced 320 SARS-CoV-2 viral genomes isolated from patients from the outpatient COVID-19 clinic in the Children's Cancer Hospital Egypt 57357 (CCHE 57357) and the Egypt Center for Research and Regenerative Medicine (ECRRM). The samples were collected between March and December 2021, covering the third and fourth waves of the pandemic. The third wave was found to be dominated by Nextclade 20D in our samples, with a small number of alpha variants. The delta variant was found to dominate the fourth wave samples, with the appearance of omicron variants late in 2021. Phylogenetic analysis reveals that the omicron variants are closest genetically to early pandemic variants. Mutation analysis shows SNPs, stop codon mutation gain, and deletion/insertion mutations, with distinct patterns of mutations governed by Nextclade or WHO variant. Finally, we observed a large number of highly correlated mutations, and some negatively correlated mutations, and identified a general inclination toward mutations that lead to enhanced thermodynamic stability of the spike protein. Overall, this study contributes genetic and phylogenetic data, as well as provides insights into SARS-CoV-2 viral evolution that may eventually help in the prediction of evolving mutations for better vaccine development and drug targets.

摘要

到目前为止,新冠病毒大流行的总体模式是一系列的浪潮;新病例激增后又下降。新型突变和变体的出现是感染增加的原因,因此对新冠病毒突变的监测以及变体进化的预测至关重要。在本研究中,我们对从埃及儿童癌症医院57357(CCHE 57357)和埃及研究与再生医学中心(ECRRM)的门诊新冠诊所患者中分离出的320个新冠病毒基因组进行了测序。样本采集于2021年3月至12月之间,涵盖了大流行的第三波和第四波。我们发现第三波样本中以Nextclade 20D为主,还有少量的阿尔法变体。发现德尔塔变体在第四波样本中占主导地位,2021年末出现了奥密克戎变体。系统发育分析表明,奥密克戎变体在基因上与大流行早期的变体最为接近。突变分析显示了单核苷酸多态性、终止密码子突变增加以及缺失/插入突变,不同的突变模式由Nextclade或世界卫生组织的变体决定。最后,我们观察到大量高度相关的突变,以及一些负相关的突变,并确定了一种普遍倾向于导致刺突蛋白热力学稳定性增强的突变。总体而言,本研究提供了遗传和系统发育数据,并深入了解了新冠病毒的进化,这最终可能有助于预测不断演变的突变,以更好地开发疫苗和确定药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/d598db3f5cf5/fmicb-14-1190133-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/d67562035037/fmicb-14-1190133-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/97a81631c8fa/fmicb-14-1190133-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/adfa1344b926/fmicb-14-1190133-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/d598db3f5cf5/fmicb-14-1190133-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/d67562035037/fmicb-14-1190133-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/394cc6f3cebf/fmicb-14-1190133-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/0ed6a5052770/fmicb-14-1190133-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/241583587618/fmicb-14-1190133-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/97a81631c8fa/fmicb-14-1190133-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/adfa1344b926/fmicb-14-1190133-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ee/10273679/d598db3f5cf5/fmicb-14-1190133-g008.jpg

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