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Review
. 2022 Dec:65:100882.
doi: 10.1016/j.drup.2022.100882. Epub 2022 Oct 3.

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

Daniele Focosi  1 , Scott McConnell  2 , Arturo Casadevall  2
Affiliations
Review

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

Daniele Focosi et al. Drug Resist Updat. 2022 Dec.

Abstract

WHO-defined SARS-CoV-2 variants of concern (VOC) drive therapeutics and vaccine development. The Omicron VOC is dominating the arena since November 2021, but the number of its sublineages is growing in complexity. Omicron represent a galaxy with a myriad of stars that suddenly rise and expand before collapsing into apparent extinction when a more fit sublineage appears. This has already happened with BA.1, BA.2, and BA.4/5 and is happening with BA.2.75. We review here the current PANGO phylogeny, focusing on sublineages with Spike mutations, and show how frequently xxxxxxxx convergent evolution has occurred in these sublineages. We finally summarize how Omicron evolution has progressively defeated the anti-Spike monoclonal antibodies authorized so far, leaving clinicians to again fall back on COVID19 convalescent plasma from vaccinated donors as the only antibody-based therapy available.

Keywords: B.1.1.529; BA.1; BA.2; BA.2.12.1; BA.2.75; BA.4; BA.4.6; BA.5; Omicron; SARS-CoV-2; Spike; VOC; Variant of concern.

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Conflict of interest statement

Conflict of Interest We declare we have no conflict of interest related to this manuscript.

Figures

Fig. 1
Fig. 1
SARS-CoV-2 S protein mutations found in Omicron variant sublineages. A) Positions on the S protein where amino acid mutations are found in different Omicron sublineages are mapped to the spike trimer structure (PBD 6VXX). The S trimer is rotated 180 degrees along the y-axis to show both faces of the long axis and 90 degrees about the x-axis to display mutations on the receptor binding domains. Positions with amino acid mutations found in all Omicron sublineages are colored green. Positions that are BA.1 and BA.2.75 strain-specific are colored blue and red, respectively, and mutations found only in BA.4/BA.5, BA.2/BA.3/BA.4/BA.5, BA.1/BA.2 and BA.1/BA.2 are colored orange, yellow, purple and white, respectively. Positions where amino acid substitutions are different across different sublineages are indicated with an asterisk. B) Instances of convergent evolution in the Omicron sublineages are highlighted in magenta on the homotrimeric S protein structure (PBD 7C2L). The domain organization of S is highlighted with RBD, NTD, S1, and S2 subunits colored black, dark grey, light grey, and white, respectively. The homotrimer is rotated 180 degrees about the y-axis to show both faces. In the top panel, the sites of convergent evolution on the S homotrimer alone are indicated. In the bottom panel, the interfaces with clinically important mAbs from 3 different classes (Focosi et al., 2022c) (cilgavimab, bebtelovimab, and sotrovimab; colored blue, dark green and light green, respectively) are displayed to highlight the importance of the positions of convergent evolution in the Omicron S protein.
See this image and copyright information in PMC

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