New insights into COVID-19 RNA variations and their implications

New Delhi : A team of scientists from top Indian
research institutes has identified variations in COVID-19 RNA and their
implications by using state-of-the-art genomic sequencing methods. The
researchers have also studied the fixation of these intra-host variations into extra-
host variations and mutations that lead to variants.

The RNA structure of the COVID-19 virus frequently undergoes minor
modifications within the host cells (‘intra-host variations’). These modifications
occur at the nucleotide level – nucleotide being the building block of the RNA
molecule. Many of these intra-host variations are caused by enzymes present in
the host cell as an immune response. Thus, many of these variations are harmless
or even destructive to the virus itself. However, some variations can enhance the
survivability of the virus, and become fixed as extra-host variations that could
potentially lead to variants of concern.

Researchers studied intra-host Single Nucleotide Variations (iSNV) using a
sequencing platform called Illumina. During Phase-I of the project in 2020,
scientists analysed the RNA structure of virus samples collected from China,
Germany, Malaysia, the United Kingdom, America, and different subpopulations
of India to map the iSNV across the RNA structure of the virus.
Tracking and understanding the fate of iSNV can help predict the variants of
concern and plan actionable interventions. This understanding helps know the
differences in individual and population responses to the infection and devise
therapeutic protocols to treat COVID infections.

Dr Mitali Mukerji, Professor and Head, Department of Bioscience &
Bioengineering, IIT Jodhpur, who co-led the study, says, “One of the most
important aspects to managing the COVID-19 pandemic is to unravel the genetic
structure of the virus and pick up early warning signatures. We observed 16,410
iSNV sites spanning the viral genome, and a high density of alterations was
present in critical areas that could alter or override the body’s ability to trigger an
immune response.”

This research was initiated at the Council of Scientific and Industrial Research-
Institute of Genomics and Integrative Biology (CSIR -IGIB, (Delhi), and was led by

IIT Jodhpur and Institute of Life Sciences (ILS), Bhubaneswar. Other collaborating
institutes are the Academy of Scientific and Innovative Research (Ghaziabad),
Council of Scientific and Industrial Research-Center for Cellular and Molecular
Biology (CSIR-CCMB), Hyderabad, and National Center for Disease Control (NCDC),
New Delhi.
Researchers observed similar patterns across populations and waves of the
pandemic. It also tracked the iSNVs over time to see if the variants produced
inside the host cells can persist outside, thereby becoming fixed as SNVs. They
found that by 30 June 2021 about 80% of the iSNV sites they had identified in
2020 became fixed as SNVs. The conversion of iSNVs to SNVs was substantiated in
Phase 2 studies that showed iSNVs were found in most of the Delta and Kappa
variants before their fixation as SNVs by February 2021.

“The evolution of SNVs from iSNVs can affect vaccine response by altering the
antibody generation in infected individuals,” says Dr. Mukerji, on the implications
of their findings. The identification of iSNVs can also help identify critical sites in
the viral RNA that are important for its survival and spread.

The study was conducted primarily by a team of computational graduates who
aspire to work in the space of Big Data in computational “omics” sciences. Among
those in the group are noteworthy, Mr. Ankit Pathak, a B.Tech in computational
sciences and Mr. Gyan Prakash Mishra who is a Master in pharmaco-informatics.
The multi-institutional team, led by Dr. Mitali Mukerji, Professor and Head,
Department of Bioscience & Bioengineering, IIT Jodhpur and Dr. Sunil Raghav,
Scientist F, Institute of Life Sciences, Bhubaneswar, plans to combine iSNV
identification protocols with whole-genome sequencing in the future to enable
more accurate models for viral epidemiology.
The results of the two-phase study have been published in the journal Nucleic
Acid Research. (India Science Wire)

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