India Identifies 19 SARS-CoV-2 Variants With One Possessing The N440K Mutation On It Gaining Prevalence In Circulation
: A new study by researchers from CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB)-India, Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Ghaziabad-India and the Kurnool Medical College-India have identified 19 New SARS-CoV-2 variants in India with one possessing the N440K Mutation. All of these strains have human host immune evading mechanisms.
The study analysis suggests that a number of genetic variants associated with immune escape have emerged not only in India but also in in global populations.
Of the 19 of the 86 genetic variants found in genomes from India, the S:N440K variant was found to have a frequency of 2.1% in India and a high prevalence in the state of Andhra Pradesh (33.8% of 272 genomes). The variant site was homplasic and the variant was found in genomes belonging to different clades and haplotypes. Time-scale analysis suggested the variant emerged in recent months. The S:N440K variant was also reported in a case of COVID-19 reinfection from North India.
The study was published on a preprint server and is currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2020.12.24.424332v1
The N440K mutation is associated with greater binding affinity with human host receptors and is associated with greater infectivity ad transmission capability.
Genomic documentation of the spread of SARS-CoV-2 across the globe has provided unique insights into the genetic variability and variants of functional consequence. In-depth studies in recent months have unraveled a wealth of information on the immune response in COVID-19 and offered insights into the development of therapeutics.
Recent investigations suggest a number of genetic variants in SARS-CoV-2 are associated with immune escape and/or resistance to antibodies. Their structural and functional features and mechanisms of immune evasion are also being extensively studied. https://pubmed.ncbi.nlm.nih.gov/33112236/
To date, the natural occurrence and genetic epidemiology of these variants across the global populations are poorly understood.
The study team was motivated by the wide availability of SARS-CoV-2 genomes from across the world and the increasing numbers of genetic variants suggested to contribute to escape from antibody inhibition.
In order to understand the genetic epidemiology of these variants in the global compendium of genomes, the study team compiled the dataset of265,079 SARS-CoV-2 from GISAID (as of 17 December 2020) apart from 1,154 genomes sequenced in-house (BioProject ID: PRJNA655577). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388101/
Genome sequences with more than 5% Ns, more than 10 ambiguous nucleotides, higher than expected divergence and mutation clusters were excluded from the analysis. After quality control, the final dataset encompassed 240,133 genomes from 133 countries. Only countries with at least 100 good quality genome submissions were considered for the analysis.
Phylogenetic analysis wa
s performed following the Nextstrain protocol for a total of 3,679 genomes, including 1,501 randomly selected genomes having these variants. https://nextstrain.org/sars-cov-2/
Next homoplasies were identified in the phylogeny using HomoplasyFinder. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412054/
Significantly, out of 86, 43 variant sites were found to be homoplasic, suggesting they could emerge independently in different genetic lineages, out of which 9 were found to be at >1% frequency in at least one of the countries analyzed.
Out of 14,222 genomes analyzed from Australia, 24 immune escape associated variants mapped to 9,895 genomes (70%). Of significant frequency was the S:S477N variant which was present in 9,541 genomes (67%) from Australia.
Interestingly high frequency of this variant was also found in a number of other countries particularly in Europe. S:N439K was also found at high frequencies in genomes from a number of countries in Europe. https://pubmed.ncbi.nlm.nih.gov/33269368/
S:N501Y, one of the variants in the recently reported emergent SARS-CoV-2 lineage from the United Kingdom, was present in a total of 290 genomes, including genomes from the United Kingdom, Australia, South Africa, USA, Denmark and Brazil. https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563
All 7 genomes from South Africa having S:N501Y also had the S:E484K variant and S:K417N was present in 2 of these genomes. https://www.krisp.org.za/publications.php?pubid=315
The ORF3a:G251V variant was also found to be prevalent across global genomes, with the highest frequencies in Hong Kong and South Korea. This variant is also one of the defining variants for the Nextstrain clade A1a (GISAID Clade V).
The study team suggests that a number of genetic variants which are associated with immune escape have emerged in global populations, some of them have been found to be polymorphic in many global datasets and a subset of variants have emerged to be highly frequent in some countries.
Homoplasy of the variant sites suggests that there could be a potential selective advantage to these variants.
Importantly further data and analysis would be needed to investigate the potential impact of such variants on the efficacy of different vaccines in these regions.
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