Evolutionary shifts in spike glycan-binding specificity suggest a possible association with host adaptation during SARS-CoV-2 Omicron evolution

Kuzuhara, Takashi; Hatakeyama, Dai

doi:10.51094/jxiv.4819

##article.authors##

Kuzuhara, Takashi Tokushima Bunri University
Hatakeyama, Dai Toho University

DOI:

https://doi.org/10.51094/jxiv.4819

キーワード:

SARS-CoV-2、 Omicron、 spike protein、 Neu5Gc、 glycan-binding、 host-adaptation

抄録

Despite extensive genomic surveillance, the evolutionary origin of the SARS-CoV-2 Omicron variant remains the subject of intense debate. Several hypotheses have been proposed, including prolonged evolution in chronically infected individuals, cryptic human circulation, and adaptation to non-human mammalian hosts. However, the molecular signatures of these host-switching events remain unclear. The glycan-binding properties of the viral surface proteins are critical determinants of host tropism and cross-species transmission. Our recent experimental evidence highlights the distinct glycan-binding specificities of the Delta and Omicron variants. Reanalysis of previously published glycan array data confirmed that the Omicron spike exhibits an expanded binding repertoire that includes N-glycolylneuraminic acid (Neu5Gc)-containing glycans, whereas the Delta spike does not. Because humans lack Neu5Gc due to the irreversible inactivation of the CMAH gene, this shift in glycan recognition suggests that SARS-CoV-2 may have experienced selective pressure in Neu5Gc-expressing mammalian hosts prior to the emergence of Omicron. Although the present analysis does not establish the evolutionary origin of Omicron, it identifies Neu5Gc recognition as a testable molecular feature that may contribute to future investigations of host adaptation and cross-species transmission.

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The authors have declared that no competing interests exist.

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引用文献

Kupferschmidt K. Where did 'weird' Omicron come from? Science 374, 1179 (2021).

Shafer M et al. Tracing the origin of SARS-CoV-2 omicron-like spike sequences detected in an urban sewershed: a targeted, longitudinal surveillance study of a cryptic wastewater lineage. The Lancet Microbe, 5, e335-e344 (2024).

Wei C et al. Evidence for a mouse origin of the SARS-CoV-2 Omicron variant. J. Genet. Genomics 48, 1111-1121 (2021).

Roemer C et al. SARS-CoV-2 evolution in the Omicron era. Nat. Microbiol. 8, 1952-1959 (2023).

Oude Munnink BB et al. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science 371, 172-177 (2021).

Chandler JC et al. SARS-CoV-2 exposure in wild white-tailed deer (Odocoileus virginianus). Proc. Natl. Acad. Sci. 118, e2114828118 (2021).

Hale VL et al. SARS-CoV-2 infection in free-ranging white-tailed deer. Nature. 602, 481–486 (2022).

Kuchipudi SV et al. Multiple spillovers from humans and onward transmission of SARS-CoV-2 in white-tailed deer. Proc. Natl. Acad. Sci. 119, e2121644119 (2022).

Li B et al. Identification of potential binding sites of sialic acids on the RBD domain of SARS-CoV-2 spike protein. Front. Chem. 9, 659764 (2021).

Unione L et al. The SARS-CoV-2 spike glycoprotein directly binds exogeneous sialic acids: A NMR view. Angew. Chem. Int. Ed. Engl. 61, e202201432 (2022).

Díaz-Salinas MA et al. Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid. Sci. Adv. 10, eadk4920 (2024).

Nguyen L et al. Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2. Nat. Chem. Biol. 18, 81–90 (2022).

Hatakeyama D et al. Glycan-binding properties of SARS-CoV-2 spike proteins: interactions with aminoglycoside antibiotics. Sci. Rep., 16, 12769 (2026).

Varki A. Colloquium paper: uniquely human evolution of sialic acid genetics and biology. Proc. Natl. Acad. Sci. 107, suppl. 2, 8939–8946 (2010).

Carabelli AM et al. SARS-CoV-2 variant biology: immune escape, transmission and fitness. Nat. Rev. Microbiol. 21, 162–177 (2023).

Holmes EC et al. The origins of SARS-CoV-2: A critical review. Cell 184, 4848–4856 (2021).

Graham RL & Baric RS. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J. Virol. 84, 3134–3146 (2010).

Guan M et al. Neu5Gc binding loss of subtype H7 influenza A virus facilitates adaptation to gallinaceous poultry following transmission from waterbirds. J. Virol. 98, e00119242024 (2024).