Chand Gyanendra Bahadur, Banerjee Atanu, Azad Gajendra Kumar
Department of Zoology, Patna University, Patna, Bihar, India.
Department of Zoology, Samastipur College, Samastipur, Bihar, India.
PeerJ. 2020 Jul 3;8:e9492. doi: 10.7717/peerj.9492. eCollection 2020.
The rapid development of the SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for effective antivirals. SARS-CoV-2 is an RNA virus that has an inherently high mutation rate. These mutations drive viral evolution and genome variability, thereby facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and the 'Wuhan wet sea food market virus' sequence to identify, if any, variation between them. Our data revealed the occurrence of seven mutations in Indian isolates of SARS-CoV-2. The secondary structure prediction analysis of these seven mutations shows that three of them cause alteration in the structure of RdRp. Furthermore, we did protein modelling studies to show that these mutations can potentially alter the stability of the RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）介导的2019冠状病毒病（COVID-19）大流行的迅速发展引发了人们对健康的重大担忧，凸显了对有效抗病毒药物的迫切需求。SARS-CoV-2是一种RNA病毒，其固有突变率很高。这些突变推动病毒进化和基因组变异性，从而使病毒能够迅速发生抗原转变以逃避宿主免疫并产生耐药性。病毒RNA依赖性RNA聚合酶（RdRp）负责病毒基因组复制和RNA合成。因此，我们比较了来自印度分离株的SARS-CoV-2的可用RdRp序列与“武汉海鲜市场病毒”序列，以确定它们之间是否存在差异。我们的数据显示，SARS-CoV-2的印度分离株出现了七个突变。对这七个突变的二级结构预测分析表明，其中三个会导致RdRp结构改变。此外，我们进行了蛋白质建模研究，以表明这些突变可能会改变RdRp蛋白的稳定性。因此，我们认为印度SARS-CoV-2分离株中的RdRp突变可能具有功能后果，会干扰针对RdRp的药理剂。
