In December, 2019, an unknown viral outbreak, with pneumonia-like symptoms was reported in China (Wuhan, Hubei Province). It caused severe respiratory distress and was fatal in many cases. This deadly zoonotic virus led the World Health Organization (WHO) to declare a pandemic and lockdown was implemented in various parts of the world to alleviate spread (Rangayasami et al., 2021). Since the pandemic began, millions of cases have been reported, all over the world. Demographic studies estimated that approximately 100,871 people have been affected in China, 52,986,307 in America, and 1,293,081 in Pakistan till todate (25 December, 2021).
SARS-CoV-2 is an RNA based viral strain, belonging to the subfamily ortho-coronavirinae, family coronaviridae and order Nidovirales (Fan et al., 2019). Its genomic sequence has 79.6% similarity with SARS-CoV and is 96% homologous to the bat corona virus RaTG13 (Zhou et al., 2020). SARS-CoV-2 has mutated over time span and altered its genomic structure. This variation impacts its spread and severity in different regions of the world (Dong et al., 2020). It follows lysogenic cycle based on RNA dependent RNA polymerase (RdRp). RdRp is composed of ORF1a, ORF1b, nsp7, nsp8 and nsp12 (a catalytic subunit), involved in virion replication and transcription (Gao et al., 2020). Recently, RdRp G671S (G15451A) mutant was observed in the delta variant strains. This variant has occurred 3,438,537 times (56.68% of all samples with NSP12 sequence) in 183 countries. The first strain with this amino acid change, collected in March 2020, was hCoV-19/Germany/BW-FR0050/2020. Kannan et al. (2021) have reported a 100% frequency of this mutation in Delta and Delta plus variant. Highest frequency (67.8%) of this mutant in RdRp of Delta variant was reported by Fan et al. (2021). (Fig. 1).
Mutation based irregularity or dysfunction in viral machinery may lead to strengthen the efficacy of infection. Apart from phylogenetic and other sequence analysis, present study aimed to investigate whether this mutation influenced the binding of drugs to the mutant RdRp, compared to the wild-type control. In this study, bioinformatics methods like molecular docking, dynamics simulation and MM/PBSA energy analysis were used to analyze the impact.