Math Renukaradhya K, Mudennavar Nayana, Javaregowda Palaksha Kanive, Savanur Ambuja
SDM Research Institute for Biomedical Sciences Shri Dharmasthala Manjunatheshwara University Dharwad India.
JMIR Bioinform Biotechnol. 2022 May 30;3(1):e37391. doi: 10.2196/37391. eCollection 2022 Jan-Dec.
A recent global outbreak of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created a pandemic and emerged as a potential threat to humanity. The analysis of virus genetic composition has revealed that the spike protein, one of the major structural proteins, facilitates the entry of the virus to host cells.
The spike protein has become the main target for prophylactics and therapeutics studies. Here, we compared the spike proteins of SARS-CoV-2 variants using bioinformatics tools.
The spike protein sequences of wild-type SARS-CoV-2 and its 6 variants-D614G, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), gamma (P.1), and omicron (B.1.1.529)-were retrieved from the NCBI database. The ClustalX program was used to sequence multiple alignment and perform mutational analysis. Several online bioinformatics tools were used to predict the physiological, immunological, and structural features of the spike proteins of SARS-CoV-2 variants. A phylogenetic tree was constructed using CLC software. Statistical analysis of the data was done using jamovi 2 software.
Multiple sequence analysis revealed that the P681R mutation in the delta variant, which changed an amino acid from histidine (H) to arginine (R), made the protein more alkaline due to arginine's high pKa value (12.5) compared to histidine's (6.0). Physicochemical properties revealed the relatively higher isoelectric point (7.34) and aliphatic index (84.65) of the delta variant compared to other variants. Statistical analysis of the isoelectric point, antigenicity, and immunogenicity of all the variants revealed significant correlation, with values ranging from <.007 to .04. The generation of a 2D gel map showed the separation of the delta spike protein from a grouping of the other variants. The phylogenetic tree of the spike proteins showed that the delta variant was close to and a mix of the bat coronavirus and MERS-CoV.
The comparative analysis of SARS-CoV-2 variants revealed that the delta variant is more aliphatic in nature, which provides more stability to it and subsequently influences virus behavior.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的新型冠状病毒肺炎（COVID-19）近期在全球爆发，引发了一场大流行，成为对人类的潜在威胁。对病毒基因组成的分析表明，刺突蛋白作为主要结构蛋白之一，促进病毒进入宿主细胞。
刺突蛋白已成为预防和治疗研究的主要靶点。在此，我们使用生物信息学工具比较了SARS-CoV-2变体的刺突蛋白。
从NCBI数据库中检索野生型SARS-CoV-2及其6种变体（D614G、α（B.1.1.7）、β（B.1.351）、δ（B.1.617.2）、γ（P.1）和奥密克戎（B.1.1.529））的刺突蛋白序列。使用ClustalX程序进行多序列比对并进行突变分析。使用多个在线生物信息学工具预测SARS-CoV-2变体刺突蛋白的生理、免疫和结构特征。使用CLC软件构建系统发育树。使用jamovi 2软件对数据进行统计分析。
多序列分析显示，δ变体中的P681R突变将一个氨基酸从组氨酸（H）变为精氨酸（R），由于精氨酸的高pKa值（12.5），相比组氨酸的pKa值（6.0），使该蛋白更具碱性。理化性质显示，与其他变体相比，δ变体的等电点（7.34）和脂肪族指数（84.65）相对较高。对所有变体的等电点、抗原性和免疫原性进行统计分析，结果显示存在显著相关性，P值范围为<.007至.04。二维凝胶图谱的生成显示δ刺突蛋白与其他变体分组分离。刺突蛋白的系统发育树表明，δ变体与蝙蝠冠状病毒和中东呼吸综合征冠状病毒（MERS-CoV）接近且混合。
对SARS-CoV-2变体的比较分析表明，δ变体本质上更具脂肪族性，这为其提供了更高的稳定性，进而影响病毒行为。
