https://doi.org/10.4081/jbr.2026.15925
Bioinformatic evidence of spike-olfactory receptor mimicry: a potential mechanism for anosmia after SARS-CoV-2 infection and vaccination
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Accepted: 20 September 2026
Published: 1 October 2026
Anosmia is one of the most common neurological symptoms to occur following infection with SARS-CoV-2, whilst olfactory disorders are rare following vaccination. The immune-mediated response against the olfactory structures could have broad implications for the proper functioning of the central nervous system, as the sense of smell is not only important for the perception of odors but is also closely interconnected with the gustatory, limbic and cognitive circuits. Molecular mimicry between viral and host proteins is one of the plausible mechanisms underlying these effects. In light of this, we carried out a systematic bioinformatic analysis to identify potential linear peptide matches between the human olfactory receptor proteome and SARS-CoV-2 proteins, focusing on the spike glycoprotein. We found multiple peptide matches between olfactory receptors and SARS-CoV-2 proteins, but only OR5H14 shared an identical hexapeptide (ISVTTE) with the spike glycoprotein, suggesting a possible mechanism underlying the rare spike-mediated post-vaccination olfactory dysfunction. This also explains why, by contrast, greater viral exposure during infection leads to a higher prevalence of anosmia. Furthermore, the shared amino acid sequence segment demonstrated antigenic-immunogenic potential. These findings support a potential role for molecular mimicry between the spike protein and OR5H14 in post-vaccination anosmia, with implications for the sensory and cognitive pathways of the central nervous system, laying the foundations for future immunological studies.
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1. Parma V, Ohla K, Veldhuizen MG, et al. More than smell: COVID-19 is associated with severe impairment of smell, taste, and chemesthesis. Chem Senses 2020;45:609-22. DOI: https://doi.org/10.1093/chemse/bjaa041
2. Boscolo-Rizzo P, Polesel J, Spinato G, et al. Predominance of an altered sense of smell or taste among long-lasting symptoms in patients with mildly symptomatic COVID-19. Rhinology 2020;58:524-5. DOI: https://doi.org/10.4193/Rhin20.263
3. Bryche B, St Albin A, Murri S, et al. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav Immun 2020;89:579-86. DOI: https://doi.org/10.1016/j.bbi.2020.06.032
4. de Melo GD, Lazarini F, Levallois S, et al. COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Sci Transl Med 2021;13:eabf8396. DOI: https://doi.org/10.1126/scitranslmed.abf8396
5. Mutiawati E, Fahriani M, Mamada SS, et al. Anosmia and dysgeusia in SARS-CoV-2 infection: incidence and effects on COVID-19 severity and mortality, and the possible pathobiology mechanisms: a systematic review and meta-analysis. F1000Res 2021;10:40. DOI: https://doi.org/10.12688/f1000research.28393.1
6. Arabzadeh Bahri R, Esmaeilpur Abianeh F, Peisepar M, et al. Anosmia or ageusia following COVID-19 vaccination: a systematic review. Ear Nose Throat J 2024;103:164S-170S. DOI: https://doi.org/10.1177/01455613241233098
7. Kawabata M, Mori E, Yanagi N, et al. Olfactory disorder after COVID-19 vaccination. Rhinology 2025;63:441-7. DOI: https://doi.org/10.4193/Rhin23.499
8. Marino Gammazza A, Légaré S, Lo Bosco G, et al. Human molecular chaperones share with SARS-CoV-2 antigenic epitopes potentially capable of eliciting autoimmunity against endothelial cells: possible role of molecular mimicry in COVID-19. Cell Stress Chaperones 2020;25:737-41. DOI: https://doi.org/10.1007/s12192-020-01148-3
9. D’Amico G, Gratie MI, Vergilio G, et al. Beyond folding: the dual life of Hsp60 in tissue homeostasis and pathophysiology. Appl Biosci 2026;5:7. DOI: https://doi.org/10.3390/applbiosci5010007
10. Angileri F, Gratie MI, Vergilio G, et al. Molecular mimicry may explain multi-organ damage in COVID-19. Autoimmun Rev 2020;19:102591. DOI: https://doi.org/10.1016/j.autrev.2020.102591
11. Marino Gammazza A, Légaré S, Lo Bosco G, et al. Molecular mimicry in the post-COVID-19 signs and symptoms of neurovegetative disorders? Lancet Microbe 2021;2:e94. DOI: https://doi.org/10.1016/S2666-5247(21)00033-1
12. Lucchese G, Flöel A. Molecular mimicry between SARS-CoV-2 and respiratory pacemaker neurons. Autoimmun Rev 2020;19:102556. DOI: https://doi.org/10.1016/j.autrev.2020.102556
13. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-15. DOI: https://doi.org/10.1056/NEJMoa2034577
14. Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 2020;586:594-9. DOI: https://doi.org/10.1038/s41586-020-2814-7
15. Jespersen MC, Peters B, Nielsen M, et al. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res 2017;45:W24-9. DOI: https://doi.org/10.1093/nar/gkx346
16. Kolaskar AS, Tongaonkar PC. A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett 1990;276:172-4. DOI: https://doi.org/10.1016/0014-5793(90)80535-Q
17. Zhang Q, Wang P, Kim Y, et al. Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res 2008;36:W513-8. DOI: https://doi.org/10.1093/nar/gkn254
18. Paul S, Weiskopf D, Angelo MA, et al. HLA class I alleles are associated with peptide-binding repertoires of different size, affinity, and immunogenicity. J Immunol 2013;191:5831-9. DOI: https://doi.org/10.4049/jimmunol.1302101
19. Paul S, Lindestam Arlehamn CS, Scriba TJ, et al. Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes. J Immunol Methods 2015;422:28-34. DOI: https://doi.org/10.1016/j.jim.2015.03.022
20. Wu C, Xu M, Dong J, et al. The structure and function of olfactory receptors. Trends Pharmacol Sci 2024;45:268-80. DOI: https://doi.org/10.1016/j.tips.2024.01.004
21. Breer H. Sense of smell: recognition and transduction of olfactory signals. Biochem Soc Trans 2003;31:113-6. DOI: https://doi.org/10.1042/bst0310113
22. DeMaria S, Ngai J. The cell biology of smell. J Cell Biol 2010;191:443-52. DOI: https://doi.org/10.1083/jcb.201008163
23. de Araujo IE, Simon SA. The gustatory cortex and multisensory integration. Int J Obes (Lond) 2009;33:S34-43. DOI: https://doi.org/10.1038/ijo.2009.70
24. Rolls ET. Taste and smell processing in the brain. Handb Clin Neurol 2019;164:97-118. DOI: https://doi.org/10.1016/B978-0-444-63855-7.00007-1
25. Stocke S, Samuelsen CL. Multisensory integration underlies the distinct representation of odor-taste mixtures in the gustatory cortex of behaving rats. J Neurosci 2024;44:e0071242024. DOI: https://doi.org/10.1523/JNEUROSCI.0071-24.2024
26. Walla P. The olfactory origins of affective processing: a neurobiological synthesis through the Walla emotion model. Life 2026;16:10086. DOI: https://doi.org/10.3390/life16010086
27. Sultan-Styne K, Toledo R, Walker C, et al. Long-term survival of olfactory sensory neurons after target depletion. J Comp Neurol 2009;515:696-710. DOI: https://doi.org/10.1002/cne.22084
28. D’Anna SE, Vitale AM, D’Amico G, et al. Autoimmunity against nucleus ambiguus is putatively possible in both long-COVID-19 and vaccinated subjects: scientific evidence and working hypothesis. Biology (Basel) 2024;13:359. DOI: https://doi.org/10.3390/biology13060359
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CRediT authorship contribution
Conceptualization, Antonella Marino Gammazza and Francesco Cappello; data curation, Antonella Marino Gammazza and Giuseppa D’Amico; writing-original draft preparation, Giuseppa D’Amico and Melania Ionelia Gratie; writing-review and editing, Antonella Marino Gammazza, Giuseppa D’Amico, Melania Ionelia Gratie; Sébastien Légaré, Francesca Angileri; figures and table preparation, Francesca Angileri and Sébastien Légaré; supervision, Antonella Marino Gammazza, Francesca Angileri, Francesco Cappello. All authors have read and agreed to the published version of the manuscript.
Supporting Agencies
Data Availability Statement
All data generated or analyzed during this study are included in this published article. The datasets used are publicly available from UniProt, NCBI, and IEDB.
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