BHUBANESWAR: Amid the third wave of the coronavirus pandemic, a new study has claimed that the
future variants of SARS-CoV-2 virus can be predicted early for actionable interventions.
In the first ever study in the country and a much-needed breakthrough, scientists analysing genomes have found out how the virus evolves with new mutations within a host and new lineages are generated.
The researchers from six prominent institutes of India - Delhi-based Institute of Genomics and Integrative Biology (IGIB), Bhubaneswar-based Institute of Life Sciences (ILS), Ghaziabad-based Academy of Scientific and Innovative Research (AcSIR), Hyderabad-based Centre for Cellular and Molecular Biology (CCMB),
Delhi-based National Centre for Disease Control (NCDC) and Indian Institute of Technology (IIT), Jodhpur conducted the important study.
They claimed the new mutated variants can be predicted through the analysis of intra-host single nucleotide variations (iSNVs) in the SARS-CoV-2 genome few months before their actual spread.
The researchers accessed samples of Covid-19 diagnosed patients sequenced during two different periods of the pandemic and studied the mutations of the virus in the genes through next-generation sequencing.
In phase I, they analysed 1,347 samples collected by June 2020 from China, Germany, Malaysia, UK, US and different regions of India to perceive a genome-wide iSNV map in SARS-CoV-2 infected populations.
They observed 16,410 iSNV sites spanning the viral genome, including residues that defined the B.1 and B.6 lineages that were prominent in the samples before June 2020.
In phase II, analysis of another set of 1,774 genomes sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) lineages appeared as iSNVs before getting fixed as variants of concern (VOCs) in the population.
A senior scientist at ILS, Dr Sunil K Raghav said that when the virus mutates within the same person (host) and generates new mutations, it can be captured in next-generation sequencing called intra-host single nucleotide variations (iSNVs).
If the frequency of some mutations increases in a virus within the same person, it can be identified by iSNV analysis and with time when the frequency increases it could lead to VOC generation like Delta, he said.
"Analysing samples sequenced in India, we found the majority of Delta and Kappa lineages to carry iSNVs before the incidence in the population. This indicates that conjoint analysis of iSNVs will provide some clues on the evolvability and prove to be an important asset in genomic surveillance. Had the analysis been done earlier, Delta could have been predicted," Raghav said.
The study revealed around 42 per cent (pc) of the iSNV sites to be reported as SNVs by 30 September 2020 in consensus sequences submitted to Global Initiative on Sharing All Influenza Data (GISAID) and it increased to around 80 pc by June 30, 2021.
In order to understand how iSNVs could impact function through amino acids substitutions, the researchers examined the mutational spectra of the spike protein in more detail, given that the initial host-viral response is triggered by the attachment of the spike protein of SARS-CoV-2 with the host ACE2 receptor, disrupting the host cell membrane and activating viral entry.
Of the 6356 annotated variants in hypervariable samples, 909 correspond to protein-coding variants within the spike protein. Amongst the 909 iSNVs, 628 were found to be non-synonymous,184 synonymous, and 67 stop-coding.
The most frequently altered variants were D614, Y91, D80, I105 and I468. The D614G mutation (one of the B.1 lineage defining variants) is near the S1/S2 cleavage site and has already been shown to be more geographically spreading than the D614 type.
They looked at other spike mutations in more detail with respect to their functional consequences and found some amino acid sites within spike seem to evolve into more than one type of variant.
Given the global spread of the infection, even within the relatively small subset of samples analysed in this study from select population groups which were collected in the first few months of the pandemic, around 70% of all the variants listed by the WHO as VOCs or VOIs by June 2021 had been recorded as an iSNV site in one or more samples.
Head of Department of Bioscience and Bioengineering at IIT-Jodhpur and former chief scientist at IGIB Prof Mitali Mukerji said the study showed that tracking and analysing iSNVs as part of the ongoing genome surveillance could be important for early identification of potential VOCs and actionable interventions.
"We also observed iSNV sites at 20 out of 23 mutations in the spike protein that have been recently reported to confer antibody resistance. These mutations can have major implications in vaccine response. Conjoint analysis with the intra-host variability would help predict the spread and infectivity of viral strains in the population," she added.
The study has been published in the recent edition of high impact peer-reviewed Nucleic Acids Research journal.