Abstract
A novel severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causing COVID-19 pandemic in humans, recently emerged and has exported in more than 200 countries as a result of rapid spread. In this study, we have made an attempt to investigate the SARS-CoV-2 genome reported from 13 different countries, identification of mutations in major coronavirus proteins of these different SARS-CoV-2 genomes and compared with SARS-CoV. These thirteen complete genome sequences of SARS-CoV-2 showed high identity (>99%) to each other, while they shared 82% identity with SARS-CoV. Here, we performed a very systematic mutational analysis of SARS-CoV-2 genomes from different geographical locations, which enabled us to identify numerous unique features of this viral genome. This includes several important country-specific unique mutations in the major proteins of SARS-CoV-2 namely, replicase polyprotein, spike glycoprotein, envelope protein and nucleocapsid protein. Indian strain showed mutation in spike glycoprotein at R408I and in replicase polyprotein at I671T, P2144S and A2798V,. While the spike protein of Spain & South Korea carried F797C and S221W mutation, respectively. Likewise, several important country specific mutations were analyzed. The effect of mutations of these major proteins were also investigated using various in silico approaches. Main protease (Mpro), the therapeutic target protein of SARS with maximum reported inhibitors, was thoroughly investigated and the effect of mutation on the binding affinity and structural dynamics of Mpro was studied. It was found that the R60C mutation in Mpro affects the protein dynamics, thereby, affecting the binding of inhibitor within its active site. The implications of mutation on structural characteristics were determined. The information provided in this manuscript holds great potential in further scientific research towards the design of potential vaccine candidates/small molecular inhibitor against COVID19.
Highlights
In the last two decades, three coronaviruses viz. severe acute respiratory syndrome coronavirus (SARS-CoV) [1], Middle-East respiratory syndrome coronavirus (MERS-CoV) [2] and Severe acute respiratory syndrome coronavirus (SARSCoV)-2 have crossed the species barrier to cause deadly pneumonia in humans
SARS-CoV-2 genome has six major open reading frames (ORFs) viz. replication enzyme coding region (ORF 1a and 1b), E gene, M gene, S gene, and N gene that are common to coronaviruses and a number of other accessory genes (ORF 3a, 6, 7a, 7b and 8) (Fig 1) [3]
Replicase polyprotein (ORF 1ab) of 13 isolates, which are most conserved in all coronaviruses shared maximum identity (87%) with SARS-CoV (NC_0047180), which is less than the threshold value (90%) for demarcation of betacoronavirus species [27, 28]
Summary
In the last two decades, three coronaviruses viz. severe acute respiratory syndrome coronavirus (SARS-CoV) [1], Middle-East respiratory syndrome coronavirus (MERS-CoV) [2] and SARSCoV-2 have crossed the species barrier to cause deadly pneumonia in humans. The current outbreak of coronavirus disease 19 (COVID-19) caused by SARS-CoV-2, was first reported in December 2019 in Wuhan, Hubei province of China [3, 4] and spread across 200 countries, infecting over 2.5 million people and killed more than 1.5 lakh as of April, 23, 2020. ORF 1a and 1b encode replication enzyme consisting 16 non-structural proteins (nsp1-16) that are highly conserved among the coronaviruses. Main protease (Mpro, known as 3CLpro) is one of the important nsp encoded by ORF 1a and 1b, play an essential role in the processing of polyproteins and control the replication of coronavirus [9, 10]. RNA-dependent RNA polymerase (RdRp) known as nsp, another important replicase catalyze the replication of RNA using viral genomic RNA template [11]
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