BENGALURU: A study by the Indian Institute of Science (IISc), Bengaluru, has revealed that mutations in the SARS-CoV-2 virus that causes Covid-19, are occurring at a higher and faster rate in Bengaluru than the national and global average.
The IISc team has also provided the first evidence of a protein that expresses itself in suppressing the body’s immune response to SARS-CoV-2 virus by using a technique called high resolution mass spectrometry.
The study of viral samples recovered from nasal secretions of consenting Covid-19-positive individuals in Bengaluru, published in the Journal of Proteome Research, found that the three Bengaluru isolates analysed had 27 mutations in the viral genomes with over 11 mutations per sample — more than both the national average of 8.4 and global average of 7.3, an institute release said.
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However, precisely how virulent these mutated SARS-CoV-2 variants are, is not yet known. Utpal Tatu, Professor in the Department of Biochemistry at IISc, who led the study, told The New Indian Express, “Virulence of a certain variant comes to light only when that variant becomes stabilised.”
Virus mutations keep happening, says IISc prof
Simply put, it means the virulence — or how lethal it is — is determined only when the particular variant is observed in more number of Covid-19 positive individuals, while the study was based on a limited number of samples taken from infected patients.
But Prof Tatu pointed out that the study was undertaken four months ago, and “it is very likely that the number of mutations now is much higher than what was found then, as mutations keep happening.”
To better understand how the virus is mutating and its protein biology, the Prof Tatu-led team carried out a comprehensive ‘proteo-genomic’ investigation — a series of analyses of SARS-CoV-2 isolates.
The genomic analysis was done using what molecular biologists call ‘next generation sequencing’ (NGS), a technology that allows rapid sequencing of the entire genome.
The phylogenetic analysis — a study of the evolutionary development of a species, a group of organisms, or a particular characteristic of an organism — found that the Bengaluru isolates are most closely related to the one from Bangladesh.
It showed that the viral isolates in India have multiple origins rather than having evolved from a single ancestral variant.
Protein suppressing human immune response discovered
The study also detected 13 different proteins – most of them previously unidentified – from clinical samples.
One such protein, the “Orf9b”, which suppresses the host’s immune response, had merely been predicted, but the IISc team has provided the first evidence of its action in impacting the human immune response to Covid-19.
The SARS-CoV-2 genome is coded for more than 25 proteins, but only a handful of these had been identified so far.
However, the IISc team discovered as many as 441 proteins unique to Covid-19 positive patients, many of which are speculated to play a key role in the body’s immune response. For this, the team carried out proteomic analysis using a technique called high resolution mass spectrometry.
“Studying viral proteins provides functional information, which is currently not well represented,” Tatu said.
“Just knowing how the virus functions is not enough. We need to put it in the context of the host,” he explained.
It was in the third analysis that his team explored how the human body responds to the virus by examining host proteins, which led to the discovery of the 441 proteins unique to Covid-19 patients.
Prof Tatu said his team is upbeat about the potential this method (high resolution mass spectrometry) has for large-scale testing.
He said proteins can be reliable markers of infections like Covid-19 because they are more abundant and stable as compared to RNA molecules on which the prevalent RT-PCR tests rely.
Sheetal Tushir, a PhD student and the study’s first author, said, “The best thing we can hope to see in this century is the use of mass spectrometry as a basic technique for diagnostics.”