Omicron and Delta variant of SARS‐CoV‐2: A comparative computational study of spike protein

Abstract

Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially those of concern, may have an impact on the virus's transmissibility and pathogenicity, as well as diagnostic equipment performance and vaccine effectiveness. Even though the SARS-CoV-2 Delta variant (B.1.617.2) emerged during India's second wave of infections, Delta variants have grown dominant internationally and are still evolving. On November 26, 2021, World Health Organization identified the variant B.1.1.529 as a variant of concern, naming it Omicron, based on evidence that Omicron contains numerous mutations that may influence its behavior. However, the mode of transmission and severity of the Omicron variant remains unknown. We used computational studies to examine the Delta and Omicron variants in this study and found that the Omicron variant had a higher affinity for human angiotensin-converting enzyme 2 (ACE2) than the Delta variant due to a significant number of mutations in the SARS-CoV-2 receptor-binding domain (RBD), indicating a higher potential for transmission. Based on docking studies, the Q493R, N501Y, S371L, S373P, S375F, Q498R, and T478K mutations contribute significantly to high binding affinity with human ACE2. In comparison to the Delta variant, both the entire spike protein and the RBD in Omicron include a high proportion of hydrophobic amino acids such as leucine and phenylalanine. These amino acids are located within the protein's core and are required for structural stability. We observed a disorder-order transition in the Omicron variant between spike protein RBD regions 468-473, and it may be significant in the influence of disordered residues/regions on spike protein stability and binding to ACE2. A future study might investigate the epidemiological and biological consequences of the Omicron variant.

Nonself Mutations in the Spike Protein Suggest an Increase in the Antigenicity and a Decrease in the Virulence of the Omicron Variant of SARS-CoV-2

“…At first glance, the present results may not seem to be consistent with recent studies on the Omicron variant, which suggested an increase in virulence [10][11][12][13][14][15][16][17][18][19][20][21][22]. These studies evaluated whether the pre-existing immunological memory induced by previous vaccines or infection continues to be effective against the Omicron variant, but in the present study, the antigenicity of the Omicron variant itself was evaluated.…”

“…Therefore, the Omicron variant may not cause severe symptoms. However, due to its high infectivity and transmissibility, as suggested by other studies [10][11][12][13][14][15][16][17][18][19][20][21][22], the Omicron variant should still be regarded with alarm.…”

“…Possible functional changes associated with mutations in the Omicron variant have already been evaluated by several computational studies. Several mutations have been localized in the receptor binding domain (RBD) of the spike (S) protein, possibly contributing to higher affinity to the ACE2 receptor and lower affinity to pre-existing infectioninduced or vaccine-induced antibodies [13][14][15]. An increase in hydrophobic amino acid residues [15] or in electrostatic interactions [16,17] introduced by mutations has been linked to potentially higher infectivity and transmissibility.…”

“…Several mutations have been localized in the receptor binding domain (RBD) of the spike (S) protein, possibly contributing to higher affinity to the ACE2 receptor and lower affinity to pre-existing infectioninduced or vaccine-induced antibodies [13][14][15]. An increase in hydrophobic amino acid residues [15] or in electrostatic interactions [16,17] introduced by mutations has been linked to potentially higher infectivity and transmissibility. Computational analyses, including a structural analysis [13], an analysis based on artificial intelligence (AI) trained with numerous experimental data [18], and an analysis with amino acid interaction (AAI) networks [19], have revealed potential resistance of the Omicron variant against pre-existing antibodies.…”

In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate

“…At the time of writing, we are witnessing the rapid replacement of the delta variant by a new variant, Omicron, which has a higher transmission capacity than all the previous variants, but also has substantial antigenic changes. Omicron has been first characterised in South Africa (B.1.1.529 lineage,"Weekly epidemiological update on COVID-19 -21 December 2021," n.d.) and exhibits the highest number of genomic mutations reported so far, especially in the spike glycoprotein where over 30 substitutions are present (Kumar et al, 2021). Such changes in the most important antigen of the virus, against which the neutralising humoral response is built, have the potential to significantly reduce the efficacy of both vaccines and therapeutic antibodies currently in clinical use (Malani et al, 2021;Taylor et al, 2021), as most of them were designed from the spike protein of the original SARS-CoV-2 strain (Baum et al, 2020;Cathcart et al, 2021;Jones et al, 2021;Kim et al, 2021).…”