SARS-CoV-2 Omicron variant: A next phase of the COVID-19 pandemic and a call to arms for system sciences and precision medicine

Abstract

Since early 2020, coronavirus diseases 2019 (COVID-19) infection pandemic/endemic is constantly surprising health experts because of continuous variations in the structures of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the form of newly emerged variants. Such mutations have exhibited high mortality and severity due to the newly emerged more infectious sites of SARS-CoV-2, making viral infection more transmissible, infectious, and severe. Recently, SARS-CoV-2 mutated to another variant, namely, Omicron (B.1.1.529), which is many times more transmissible and infectious than existed deadly Delta variants of the virus. This severity is closely correlated to a larger number of mutations observed in the receptor-binding domain of the spike protein of the Omicron-SARS-CoV-2. Considering severity, Omicron has been declared as variant of concerns by the World Health Organization and within days from its emergence, Omicron infection has spread globally, increased hospitalization, exhibited more severity for the young generation, invaded defense mechanism of natural immunity, not responsive to the available vaccines. Such circumstances resonated with the efficiency of available strategies established to manage COVID-19 intelligently and successfully. To explore these aspects, this perspective article carefully and critically summarizes the Omicron's origin, structure, pathogenesis, impact health along with health systems, and experts' recommendations to manage it successfully.

Keywords: COVID‐19 infection; Omicron; SARS‐CoV‐2 mutations; diagnostics; nanomedicine; precision medicine.

FIGURE 1

Illustration of Omicron mutation and its effects on health, infection progression, and COVID‐19 management aspects. (A) The main spike mutations found from the isolated viruses of Omicron B.1.1.529, Copyright permission Nature 2022. (B) Phylogenetic analysis of SARS‐CoV‐2 clusters mutation (Source: https://nextstrain.org/groups/neherlab/ncov/21K.Omicron?l = radial). (C) Total 50 mutations in which 30 of them at spike protein causing transmissivity and severe health effect. (D) Illustration of spike protein mutation of Omicron (right side) in comparison of Delta (left side), Copyright permission Wiley 2022. (E) Frequency of infection over the time, since December 2021 Omicron is contributing 99%, and Delta is around 1% (Source: https://nextstrain.org/groups/neherlab/ncov/21K.Omicron?l = radial). (F) The potential impact of Omicron (B.1.1.529) causing enhanced transmission, infectivity, and resistance to therapeutics, especially vaccines. Figure F is created using BioRender.com

FIGURE 2

Omicron spike protein–human ACE2 complex interactions. (A) Cryo‐EM structural map of the Omicron spike protein in complex with human ACE2 at 2.45Å resolution. Human ACE2 is colored in blue, while various shades of purple are used for three different promoters. (B) Cryo‐EM structural map of the Omicron spike RBD in complex with ACE2 at 2.66 Å resolution, where (C) shows the fitted atomic model of Cryo‐EM density mesh at the highlighted inset of (B). (D–F) Comparison of the RBD–ACE2 interface between the Omicron (top panels) and Delta (bottom panels) variants reveals that in the case of Omicron variant, new interactions are formed, which is attributed to new mutations, namely, Q493R, G496S, and Q498R, Copyright permission Science 2022. (G,H) Omicron variant RBD shows increased binding to human ACE2. (G) ACE2 binding to six RBD variants, and comparison between their single‐cycle kinetics surface plasmon resonance (SPR) analysis. (H) Quantification of human ACE2 binding data, Copyright permission Nature 2022

FIGURE 3

Recommendations to manage Omicron‐SARS‐CoV‐2 variant. Experts recommend managing Omicron infection by taking every precaution seriously, increasing rapid and selective testing of Omicron, tracking of infected and postinfection patients to understand pathogenesis and cross‐reactivity, fostering novel therapeutics to recognize and eradicate Omicron virus, and precision medicine for individuals by employing AI, big data reservoirs, bioinformatic system, advanced in vitro 3D models (microfluidic systems, organoids, etc.), and subtype sciences. Figure created using BioRender.com