One of the most important proteins for COVID-19 pathogenesis in SARS-CoV2 is the ORF3a protein which is the largest accessory protein among others accessory proteins coded by coronavirus genome. The major roles of the protein include virulence, infectivity, ion channel activity, morphogenesis and virus release. The coronavirus, SARS-CoV2 is continuously evolving naturally and thereby the encoded proteins are also mutating rapidly. Therefore, critical study of mutations in ORF3a is certainty important from the pathogenetic perspective. Here, a sum of 175 various non-synonymous mutations in the ORF3a protein of SARS-CoV2 are identified and their corresponding effects in structural stability and functions of the protein ORF3a are studied. Broadly three different classes of mutations, such as neutral, disease and mixed (neutral and disease) type mutations were observed. Consecutive mutations in some ORF3a proteins are established based on timeline of detection of mutations. Considering the amino acid compositions over the ORF3a primary protein sequences, twenty clusters are detected based on K-means clustering method. Our findings on 175 novel mutations of ORF3a proteins will extend our knowledge of ORF3a, a vital accessory protein in SARS-CoV2, which would assist to enlighten on the pathogenicity of this life-threatening COVID-19.

中文翻译：

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SARS-CoV2 ORF3a蛋白错义突变的病因学观点

ORF3a蛋白是SARS-CoV2中COVID-19发病机理中最重要的蛋白之一，它是冠状病毒基因组编码的其他辅助蛋白中最大的辅助蛋白。该蛋白的主要作用包括毒性，传染性，离子通道活性，形态发生和病毒释放。冠状病毒SARS-CoV2不断自然进化，因此编码的蛋白质也迅速突变。因此，从致病性的角度来看，对ORF3a突变的关键研究必不可少。在此，鉴定出SARS-CoV2的ORF3a蛋白中的175个各种非同义突变，并研究了它们对蛋白ORF3a的结构稳定性和功能的相应影响。大致分为三类不同的突变，例如中性，观察到疾病和混合（中性和疾病）类型的突变。基于突变检测的时间线，可以确定某些ORF3a蛋白中的连续突变。考虑到ORF3a一级蛋白质序列上的氨基酸组成，基于K-均值聚类方法检测到二十个簇。我们对ORF3a蛋白的175个新突变的发现将扩展我们对ORF3a的了解，ORF3a是SARS-CoV2中的重要辅助蛋白，将有助于启发这种威胁生命的COVID-19的致病性。