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How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling

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Abstract

Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.

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Authors and Affiliations

  1. Division of Ophthalmology, Ümraniye Trn. And Rch. Hospital, Istanbul, Turkey

    Işıl Kutlutürk

  2. Ophthalmology Department, University of Health Science, Derince Training and Research Hospital, Izmit-Kocaeli, Turkey

    Ecem Önder Tokuç

  3. Ophthalmology Department, Kocaeli University School of Medicine, Izmit-Kocaeli, Turkey

    Levent Karabaş

  4. Eyegnos Consulting, Bern, Switzerland

    René Rückert

  5. Diagen Biotechnology, Ankara, Turkey

    Mücahit Kaya

  6. Koşuyolu High Specialization Education and Research Hospital, Istanbul, Turkey

    Ali Karagöz

  7. Inselspital, University Hospital Bern, Bern, Switzerland

    Marion R Munk

  8. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Marion R Munk

  9. Augenarzt-Praxisgemeinschaft Gutblick AG, Bern, Switzerland

    Marion R Munk

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  1. Işıl Kutlutürk
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Contributions

Conception and design of study: IKK, LK, MK

Acquisition of data: IKK, MK

Analysis and/orinterpretation of data: IKK, MK, LK

Drafting the manuscript: IKK, EOT, LK, MM

Revising the manuscript critically for important intellectual content: IKK, LK, MM, RR

Approval of the version of the manuscript to be published: IKK, EOT, LK, MM, RR, AK, MK

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Correspondence to Işıl Kutlutürk.

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Key messages

1. This research study evaluated potential immune molecular mimicry between the epitopes on the SARS-CoV19 S protein and retinal vascular endothelial cell proteins.

2. Bioinformatics was used to identify sequence similarities for potential immune response against the SARS-CoV19.

3. Significant protein sequence similarities between SARS-CoV19 and S-protein were found.

4. Retinal vascular endothelial proteins may have a risk of being targets of autoimmune attacks after infection with SARS-CoV19.

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Kutlutürk, I., Tokuç, E.Ö., Karabaş, L. et al. How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling. Immunol Res 72, 50–71 (2024). https://doi.org/10.1007/s12026-023-09412-1

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