The causative agent of COVID-19 is a novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV-2), which has emerged as a pandemic of global concern. Considering its rapid transmission, WHO has declared public health emergency on 11th March 2020 worldwide. SARS-CoV-2 is a genetically diverse positive sense RNA virus that typically exhibit high rates of mutation than DNA viruses. Higher rates of mutation bring higher genomic variability which may lead to viral evolution and enabling viruses to evade the pre-existing immunity of host and quickly acquire drug resistance properties. The objective of our study was to compare the SARS-CoV-2 RdRp sequences of Indian SARS-CoV-2 isolates with those of Wuhan type virus. A total of 384 point mutations were detected from 488 sequence of the RdRp protein of Indian SARS-CoV-2 genome, out of which seven were used for subsequent study. Furthermore, prediction of secondary structure, protein modeling and its dynamics were performed which revealed that seven mutations (R118C, T148I, Y149C, E802A, Q822H, V880I and D893Y) significantly altered the stability and flexibility of RdRp protein. Present study was therefore, undertaken to analyze the variations occurring in RdRp due to multiple mutations leading to the alterations in the structure and function of RNA-dependent RNA polymerase which is essential for the replication /transcription of this virus and hence can be utilized as a promising therapeutic target to curb SARS-CoV-2 infections.

中文翻译：

---

SARS-CoV-2 RNA 依赖性 RNA 聚合酶突变的鉴定和表征作为有前途的抗病毒治疗靶点。

COVID-19 的病原体是一种新型 β 冠状病毒或严重急性呼吸系统综合症冠状病毒 (SARS-CoV-2)，已成为全球关注的大流行病。考虑到其快速传播，世卫组织于 2020 年 3 月 11 日宣布全球进入公共卫生紧急状态。SARS-CoV-2 是一种遗传多样性的正义 RNA 病毒，通常表现出比 DNA 病毒高的突变率。更高的突变率带来更高的基因组变异性，这可能导致病毒进化并使病毒能够逃避宿主预先存在的免疫力并迅速获得耐药性。我们研究的目的是比较印度 SARS-CoV-2 分离株与武汉型病毒的 SARS-CoV-2 RdRp 序列。印度SARS-CoV-2基因组RdRp蛋白的488个序列共检测到384个点突变，其中七个用于后续研究。此外，对二级结构、蛋白质建模及其动力学的预测表明，七个突变（R118C、T148I、Y149C、E802A、Q822H、V880I 和 D893Y）显着改变了 RdRp 蛋白的稳定性和灵活性。因此，本研究旨在分析由于多重突变导致 RdRp 发生的变异，这些变异导致 RNA 依赖性 RNA 聚合酶的结构和功能发生改变，这对于该病毒的复制/转录至关重要，因此可用作有望遏制 SARS-CoV-2 感染的治疗靶点。Y149C、E802A、Q822H、V880I 和 D893Y) 显着改变了 RdRp 蛋白的稳定性和灵活性。因此，本研究旨在分析由于多重突变导致 RdRp 发生的变异，这些变异导致 RNA 依赖性 RNA 聚合酶的结构和功能发生改变，这对于该病毒的复制/转录至关重要，因此可用作有望遏制 SARS-CoV-2 感染的治疗靶点。Y149C、E802A、Q822H、V880I 和 D893Y) 显着改变了 RdRp 蛋白的稳定性和灵活性。因此，本研究旨在分析由于多重突变导致 RdRp 发生的变异，这些变异导致 RNA 依赖性 RNA 聚合酶的结构和功能发生改变，这对于该病毒的复制/转录至关重要，因此可用作有望遏制 SARS-CoV-2 感染的治疗靶点。