Hossain Mohammad Uzzal, Ahammad Ishtiaque, Bhattacharjee Arittra, Chowdhury Zeshan Mahmud, Hossain Emon Md Tabassum, Chandra Das Keshob, Keya Chaman Ara, Salimullah Md
Department of Pharmacology, University of Oxford Oxford OX1 3PT UK.
Bioinformatics Division, National Institute of Biotechnology Ganakbari, Ashulia, Savar Dhaka-1349 Bangladesh.
RSC Adv. 2021 Dec 3;11(61):38868-38879. doi: 10.1039/d1ra05327b. eCollection 2021 Nov 29.
Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 has already killed more than one million people worldwide. Since novel coronavirus is a new virus, mining its genome sequence is of crucial importance for drug/vaccine(s) development. Whole genome sequencing is a helpful tool in identifying genetic changes that occur in a virus when it spreads through the population. In this study, we performed complete genome sequencing of SARS-CoV-2 to unveil the genomic variation and indel, if present. We discovered thirteen (13) mutations in Orf1ab, S and N gene where seven (7) of them turned out to be novel mutations from our sequenced isolate. Besides, we found one (1) insertion and seven (7) deletions from the indel analysis among the 323 Bangladeshi isolates. However, the indel did not show any effect on proteins. Our energy minimization analysis showed both stabilizing and destabilizing impact on viral proteins depending on the mutation. Interestingly, all the variants were located in the binding site of the proteins. Furthermore, drug binding analysis revealed marked difference in interacting residues in mutants when compared to the wild type. Our analysis also suggested that eleven (11) mutations could exert damaging effects on their corresponding protein structures.
由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的冠状病毒病 19(COVID-19)已在全球造成超过 100 万人死亡。由于新型冠状病毒是一种新病毒,挖掘其基因组序列对于药物/疫苗研发至关重要。全基因组测序是识别病毒在人群中传播时发生的基因变化的有用工具。在本研究中,我们对 SARS-CoV-2 进行了全基因组测序,以揭示基因组变异和插入缺失(如果存在)。我们在开放阅读框 1ab(Orf1ab)、刺突蛋白(S)和核衣壳蛋白(N)基因中发现了 13 个突变,其中 7 个是我们测序分离株中的新突变。此外,在 323 株孟加拉国分离株的插入缺失分析中,我们发现了 1 个插入和 7 个缺失。然而,插入缺失对蛋白质没有任何影响。我们的能量最小化分析表明,根据突变情况,对病毒蛋白既有稳定作用也有不稳定作用。有趣的是,所有变体都位于蛋白质的结合位点。此外,与野生型相比,药物结合分析显示突变体中相互作用残基存在显著差异。我们的分析还表明,11 个突变可能对其相应的蛋白质结构产生破坏作用。