Identification of novel mutations in the methyltransferase complex (Nsp10-Nsp16) of SARS-CoV-2

Abstract

A recent outburst of the pandemic caused by a member of the coronaviridae family identified as SARS-CoV-2. The highly contagious nature of the virus allows it to spread rapidly worldwide and caused severe healthcare and economic distress. So far, no proper line of treatment or vaccines has been available against SARS-CoV-2. Since, the infected people rapidly increased, causing the saturation of healthcare systems with coronavirus disease (COVID-19) patients. As the virus spread to new locations it also acquired various mutations. Here, in this study, we focused on identifying mutations in one of the crucial complex of SARS-CoV-2, the Nsp10-Nsp16 2'-O-methyltransferase complex. This complex plays indispensable role in the post-transcriptional modifications of viral RNA by its capping. We analysed 208 sequences of Nsp10-Nsp16 reported from India and compared with first reported sequence from Wuhan, China. Our analysis revealed a single mutation in Nsp10 and five mutations in Nsp16 protein. We also show that these mutations are leading to alteration in the secondary structure of Nsp10-Nsp16. Further, the protein modelling studies revealed that the mutation of both Nsp10-Nsp16 impacts the protein dynamicity and stability. Altogether, this study provides novel insights into the variations observed in the proteins of SARS-CoV-2 that might have functional consequences.

Keywords: COVID-19; India; Infectious diseases; Mutations; Nsp10-Nsp16; SARS-CoV-2.

Fig. 1

Mutational analysis of Nsp10 and Nsp16. The amino acid sequences of 208 Indian SARS-CoV-2 were compared with first reported sequence from Wuhan, China. The mutations are marked in the schematic diagram of Nsp10 (A) and Nsp16 (B).

Fig. 2

Prediction of secondary structure of Nsp10 and Nsp16. The amino acid sequences near the mutation site were uploaded on CFSSP web tool that predict secondary structure. Each panel (A–F) shows the secondary structure of the wild type and mutated input sequences. The panel (i) represents the wild type or Wuhan sequence while panel (ii) represents the mutated Indian Sequence. The mutation site is highlighted in the rectangular box. The variation observed in the secondary structure between Wuhan and Indian sequence is highlighted by dashed box.

Fig. 3

The visual representation of protein dynamicity. Each panel (A–F) demonstrates the individual mutations identified from Indian SARS-CoV-2 isolates. The gain in molecular flexibility is represented by red colour and the increase in rigidity is represented by red colour. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Analysis of intramolecular interactions contributed by wild type and mutant residues. (A–F) represent the mutations of Nsp 10 and Nsp16 as shown in respective panels. Each panel has wild type and mutant residues highlighted in light green colour. The intramolecular interactions made by mutant and wild type residues are also highlighted. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)