Study finds patterns in mutations of SARS-CoV‑2

Lekha Bandopadhyay

Emerging dominant strains of the coronavirus are a cause of concern as they impact the course of the pandemic, prompting scientists to track the mutation patterns of the virus closely. In this collaborative study, an analysis of the SARS-CoV‑2 global genomic database revealed the trends of point-mutations occurring in the virus.

Viral mutations

Viruses are constantly mutating, and that is how they evolve and adapt to survive. Viral mutations arise due to the error-prone system they use for copying and propagating their genome. Mutating agents present in the immediate environment can also influence the virus to change. The mutations occurring in SARS-CoV‑2 have been a cause of concern. Hence, studying these mutations is all-important to remain aware of emerging dominant variants. 

A collaborative study led by Ranadhir Chakraborty, Professor, North Bengal University, Siliguri, and Wriddhiman Ghosh, Associate Professor, Bose Institute, Kolkata, analysed SARS-CoV‑2 genomes deposited till 21 August 2020 in the global viral genomic database (GISAID).

The researchers tried to understand the trends in terms of the nature, frequency, and distribution of viral mutations across 71703 viral sequences reported from countries around the world and compared them with the genetic sequence of the earliest SARS-CoV‑2 strain reported from Wuhan, China. The team used computational tools to track and compare mutations in the viral genome.

The researchers then extended the analysis to key viral genes. Their investigation revealed the predominance of certain missense’ mutations among the genes that code for viral envelope structures like the spike protein. Missense mutations have the potential to alter the function of a protein by replacing an amino acid of a protein with an incorrect one. These changes may or may not affect the performance of the protein. And if the structural change turns out to provide an advantage to the virus for surviving in challenging situations, then these specific mutations get selected over successive generations to become the dominant strains in a viral community. 

The researchers observed that the structural proteins known as ORF3a and ORF7a were most prone to mutation. While ORF3a has a role in regulating virulence and transmissibility, ORF7a is involved in modulating the human immune response. 

Chakraborty says, This implies vigorous molecular manoeuvring by the virus to augment its virulence potentials, escape human immunity, and ensure enhanced transmissibility.” Their observations were later given credence when several such missense mutations in the spike protein gene were identified in the emerging variants with increased transmissibility like the UK strain (B.1.1.7) and the South African variant (501Y.V2), adds Chakraborty. 

The researchers then analysed the mutations at the single nucleotide level. Nucleotides are the building blocks of genes and come in four varieties – cytidine ( C), uridine (U), guanosine (G) and adenosine (A). Single nucleotide mutations usually replace one type of nucleotide with another. The researchers observed that there was a predominance of two specific nucleotide conversions. One of these was a C to U conversion, and the other was a G to U. 

The researchers say that one driving factor for the high occurrence of these conversions could be due to the errors occurring while the virus replicates inside a human cell. In a few preliminary observations, the researchers also noticed that C‑U conversions occurred in environments that had a high content of UV irradiations and chemicals like bisulfites. They suggest that indiscriminate use of germicidal and sanitising agents could possibly act as an external trigger for mutations. 

Bornali Bhattacharjee, Ramanujan Fellow, National Institute of Biomedical Genomics, Kalyani, West Bengal, who was not connected with this study, comments that The higher frequencies of C‑U and G‑U transitions as observed in this article have also been observed by our group and a few others.”

This study brings attention to the need for multifaceted surveillance of the emerging viral variants of the SARS-CoV‑2 genome and their plausible triggers to stay a step ahead in tracking high-frequency mutations.