From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants

Abstract

Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) affected negatively the national health systems' endurance worldwide. SARS-Cov-2 virus belongs to lineage b of beta-CoVs demonstrating a strong phylogenetic similarity with BatCoVRaTG13 type. Spike (S) glycoprotein projections -consisting of two subunits S1/S2- provide a unique crown-like formation (corona) on virion's surface. Concerning their functional role, S1 represents the main receptor-binding domain (RBD), whereas S2 is involved in the virus-cell membrane fusion mechanism. On Nov 26th 2021, WHO designated the new SARS-CoV-2 strain - named Omicron, from letter ''όμικρον'' in the Greek alphabet - as a variant of concern (B.1.1529 variant). Potentially this new variant is associated with high transmissibility leading to elevated infectivity and probably increased re-infection rates. Its impact on morbidity/mortality remains under investigation. In the current paper, analyzing and comparing the alterations of SARS-CoV-2 S RNA sequences in the defined variants (Alpha to Omicron), we observed some interesting findings regarding the S1-RBD/S2 mutation/deletion equilibrium that maybe affect and modify its activity.

Keywords: COVID-19; Genome; Mutations; RNA; SARS-CoV-2; Variants.

Fig. 1

Schematic, algorithmic representation of the SARS-CoV-2 variants landscape. Specific combinations of mutations and deletions are recognized. Critical deletions affect exclusively the non-RBD S1 region (ΔΗ69/ΔV70/Δ156/Δ157/ΔΥ144/ ΔL242/ΔΑ243/ΔL244) increasing virus transmission ability/infectivity affecting also negatively the immune response levels to neutralizing antibodies (decreased serum neutralization titles). D614G is the dominant and highly conserved substitution, whereas N501Y/ E484K-Q/ K417N/T/ L452R mutations are very important. del/ D614G/ E484Q combination in delta variant seems to be unique leading COVID-19 to a specific disease phenotype. A710V/V1176F/T716I/T1027/D1118H is the most important mutations in the S2 region. Omicron variant is characterized by an ‘’exotic’’ combination of many mutations, deletions and one novel insertion.