Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility
Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility
复制标题
DOI：
10.1007/s12038-020-00046-1
复制
发表时间：
2020-06-04
影响因子：
2.9
通讯作者：
Das, Saumitra
中科院分区：
文献类型：
--
作者：
Maitra, Arindam;Sarkar, Mamta Chawla;Das, Saumitra
从东印度感染者的鼻咽和口咽拭子样本中进行了SARS-CoV-2基因组的直接大规模平行测序。其中7株属于A2a分支，1株属于B4分支。还检测到了A2a分支特有的特定突变，包括依赖RNA的RNA聚合酶中的P323L和Spike糖蛋白中的D614G。此外，我们的数据揭示了存在非同义突变的新的亚克隆的出现，即。S蛋白(S)中的G1124V、核衣壳(N)蛋白中的R203K和G204R。N蛋白突变位于参与病毒衣壳形成的SR富集区，S蛋白突变位于S-2结构域，该结构域参与触发病毒与宿主细胞膜的融合。观察到这些突变与新冠肺炎阳性病例的旅行或接触史之间存在有趣的相关性。这些突变还预测了miRNA结合和结构随后的变化。更重要的是，还讨论了突变D614G(位于S-D结构域)和G1124V(位于S-2亚基)对S蛋白结构稳定性的可能影响。结果报告首次鸟瞰了东印度SARS-CoV-2基因组突变的积累情况。
Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S-2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S-D domain) and G1124V (in S-2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.