An in-silico study of the mutation-associated effects on the spike protein of SARS-CoV-2, Omicron variant

Abstract

The emergence of Omicron (B.1.1.529), a new Variant of Concern in the COVID-19 pandemic, while accompanied by the ongoing Delta variant infection, has once again fueled fears of a new infection wave and global health concern. In the Omicron variant, the receptor-binding domain (RBD) of its spike glycoprotein is heavily mutated, a feature critical for the transmission rate of the virus by interacting with hACE2. In this study, we used a combination of conventional and advanced neural network-based in silico approaches to predict how these mutations would affect the spike protein. The results demonstrated a decrease in the electrostatic potentials of residues corresponding to receptor recognition sites, an increase in the alkalinity of the protein, a change in hydrophobicity, variations in functional residues, and an increase in the percentage of alpha-helix structure. Moreover, several mutations were found to modulate the immunologic properties of the potential epitopes predicted from the spike protein. Our next step was to predict the structural changes of the spike and their effect on its interaction with the hACE2. The results revealed that the RBD of the Omicron variant had a higher affinity than the reference. Moreover, all-atom molecular dynamics simulations concluded that the RBD of the Omicron variant exhibits a more dispersed interaction network since mutations resulted in an increased number of hydrophobic interactions and hydrogen bonds with hACE2.

Evolutionary trajectory of receptor binding specificity and promiscuity of the spike protein of SARS-CoV-2

“…Thus, experimental analyses of the association kinetics and thermodynamics suggests that evolution of SARS-CoV-2 is accompanied by a marked reduction in the molecular dynamics of the RBD. This finding is in accordance with several in silico studies showing that RBD-o decreases its conformational dynamics as compared to RBD-Wuhan and other VOCs 9, 37–39 .…”

“…Our experimental data dedicated on analyses of binding forces implicated in ACE2 recognition by the RBD supported the result from thermodynamic analyses and showed a qualitative shift in the type of non-covalent interactions in case of RBD-o. The computation analyses further corroborated these experimental data and unraveled that the electrostatic forces have the highest favorable contribution to the free energy of binding in case of the interaction of RBD-o 24, 29, 37 .…”

“…Our experimental data dedicated on analyses of binding forces implicated in ACE2 recognition by the RBD supported the result from thermodynamic analyses and showed a qualitative shift in the type of non-covalent interactions in case of RBD-o. The computation analyses further corroborated these experimental data and unraveled that the electrostatic forces have the highest favorable contribution to the free energy of binding in case of the interaction of RBD-o 24,29,37 . This remodeling in the binding mechanism could well be explained by the available structural data which have demonstrated that as result of accumulation of mutations the binding surface of RBD-o increases significantly its overall positive charge (Fig.…”

Laboratory and field evaluation of the STANDARD Q and Panbio™ SARS-CoV-2 antigen rapid test in Namibia using nasopharyngeal samples

“…The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) identified originally in China has now become a public health concern throughout the world, and now we are dealing with emerging variants of concern (VOCs) of which some are more infectious compared to the founder virus including the current circulating Omicron variant [ 1 – 3 ]. Reverse transcription polymerase chain reaction (RT-PCR) is the laboratory gold standard method to detect SARS-CoV-2 in people with coronavirus disease 2019 (COVID-19).…”

Comparative Dynamics of Delta and Omicron SARS-CoV-2 Variants across and between California and Mexico

“…The observed differences in the spatial invasion of the two major VOCs may be explained by a combination of viral and structural/behavioral factors. The shorter duration of the Omicron wave and time to peak migration may be a function of the increased transmissibility of the Omicron variant compared to the Delta variant, which may be a function of the increased affinity of the Omicron spike to the ACE2 receptor or overall hydrophobicity of the Omicron spike [ 32 , 33 , 34 ]. In addition to differences in variant characteristics (such as per-contact transmissibility, duration of infectiousness, and immune evasion [ 35 , 36 ]), local circulation and variant replacement dynamics are likely affected by human mobility but also by spatiotemporal heterogeneity in various structural factors (e.g., access and coverage of vaccinations) that need to be considered.…”