Identification and characterization of mutations in the SARS-CoV-2 RNA-dependent RNA polymerase as a promising antiviral therapeutic target

Abstract

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.