An in silico analysis of early SARS-CoV-2 variant B.1.1.529 (Omicron) genomic sequences and their epidemiological correlates

Abstract

Background: A newly emerged SARS-CoV-2 variant B.1.1.529 has worried health policymakers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) has designated it as a global variant of concern (VOC) and has named as Omicron. A surge in new COVID-19 cases has been reported from certain geographical locations, primarily in South Africa (SA) following the emergence of Omicron. Materials and methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID (until 2021-12-6) to predict the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-29 Nov 2021) with the current epidemiological data (new COVID-19 cases and deaths) from SA to understand whether the Omicron has an epidemiological advantage over existing variants. Results: Compared to the current list of global VOCs/VOIs (as per WHO) Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with Alpha variant for the complete sequence as well as for RBM. The mutations were found primarily condensed in the spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to -0.97) in the sequences reported from SA post-emergence of the new variant, later showing a decrease. There has been a steep rise in the new COVID-19 cases in parallel with the increase in the proportion of Omicron since the first case (74-100%), on the contrary, the incidences of new deaths have not been increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58). Conclusions: Omicron may have greater immune escape ability than the existing VOCs/VOIs. However, there are no clear indications coming out from the predictive mutational analysis that the Omicron may have higher virulence/lethality than other variants, including Delta. The higher ability for immune escape may be a likely reason for the recent surge in Omicron cases in SA.

GenomeBits insight into omicron and delta variants of coronavirus pathogen

“…The main difference between both comparative genomics approaches is that changes via Eq (1) can be analysed and characterised at each single A,C,G,T nucleotide level. We found a kind of 'ordered' (constant) to 'disordered' (peaked) phase transition phenomena around the NSP5 polymerase within the open reading frames ORF1a region [1,2], up to the nucleotide region of the S-Protein (coloured clear blue area).…”

“…This is important because single nucleotide polymorphisms are the most common genomic variations. The figure illustrate a kind of ‘ ordered ’ (constant) to ‘ disordered ’ (peaked) transition phenomena around the NSP-5 polymerase within the open reading frames ORF1a region [11,12], up to the nucleotide region of the S-Protein (colored clear blue area).…”

“…The delta and omicron variants share some parts of their structures [11,12]. Both variants have common mutations, i.e., amino acid changes in the building blocks that conform the spike protein (D614G mutation), and different mutations elsewhere (the P323L mutation in the NSP12 polymerase and the C241U nucleotide mutation in the 5’ untranslated region).…”

GenomeBits insight into omicron and delta variants of coronavirus pathogen

“…This is important because single nucleotide polymorphisms are the most common genomic variations. The figure illustrate a kind of ‘ordered’ (constant) to ‘disordered’ (peaked) transition phenomena around the NSP-5 polymerase within the open reading frames ORF1a region [ 10 , 11 ], up to the nucleotide region of the S-Protein (colored clear blue area).…”

“…The delta and omicron variants share some parts of their structures [ 10 , 11 ]. Both variants have common mutations, i.e ., amino acid changes in the building blocks that conform the spike protein (D614G mutation), and different mutations elsewhere (the P323L mutation in the NSP12 polymerase and the C241U nucleotide mutation in the 5’ untranslated region).…”