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

Background

A newly emerged SARS-CoV-2 variant B.1.1.529 has worried the health policy makers 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 have 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 2021-12-10) 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. The mutations present at the receptor binding domain (RBD) of the variants were assessed using an open analysis pipeline which integrates a yeast-display platform with deep mutational scanning. Further, 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-10 ^th Dec, 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 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 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.

Highlights

• Higher immune escape ability than the existing VOCs/VOIs

• No clear indications of increased affinity for ACE2 binding

• Driving a new COVID-19 wave in South Africa

• Outcompeting Delta variant

• Currently, no clear evidence for increased virulence/lethality