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SARS-CoV-2 nucleocapsid protein forms complexes with soluble complement regulatory proteins that can bind to the virion
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  • Published: 29 January 2026

SARS-CoV-2 nucleocapsid protein forms complexes with soluble complement regulatory proteins that can bind to the virion

  • Jakub Víglaský1,
  • Katarína Bhide1,
  • Lea Talpasova1,
  • Ľubica Fialová2 &
  • …
  • Mangesh Bhide1,2 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biochemistry
  • Diseases
  • Immunology
  • Microbiology
  • Molecular biology

Abstract

The SARS-CoV-2 nucleocapsid protein has been detected in the plasma of COVID-19 patients, and its levels in the plasma correlate with the severity of the disease. It is also an immunomodulatory protein, triggering the release of proinflammatory cytokines. Complement system dysregulation in COVID-19 patients led us to hypothesize that either nucleocapsid protein or spike protein might interact with the proteins of the complement system, mainly complement regulatory proteins (CRPs). We demonstrate that the nucleocapsid protein, but not the spike protein, binds to multiple CRPs, including C1-inhibitor, C4-binding protein, factor H, and vitronectin. The nucleocapsid protein binds to both the recombinant spike protein and the SARS-CoV-2 virions. We further demonstrated that the virion-nucleocapsid-CRP complex could be formed. Recruitment of the CRPs on SARS-CoV-2 virion mediated by nucleocapsid protein deserves further investigation to reveal complement modulation strategies of SARS-CoV-2.

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Data availability

Data generated in this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Ing. Martina Cepková and Ing. Viera Rusnáková for their technical assistance.

Funding

Research was funded by research projects VEGA 1/0381/23 and APVV-22-0084. A part of the work was also funded from the project awarded to Jakub Víglaský as a doctoral fellow (NextGenerationEU through the Recovery and Resilience Plan for Slovakia project No. 09I03-03-V05-00017).

Author information

Authors and Affiliations

  1. Laboratory of Biomedical Microbiology and Immunology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, Košice, 041 81, Slovakia

    Jakub Víglaský, Katarína Bhide, Lea Talpasova & Mangesh Bhide

  2. Institute of Neuroimmunology, Slovak Academy of Sciences v. v. i, Dúbravská cesta 9, 845 10 , Bratislava, Slovakia

    Ľubica Fialová & Mangesh Bhide

Authors
  1. Jakub Víglaský
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  2. Katarína Bhide
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Contributions

JV and MB designed an experimental plan. J.V. and M.B. prepared the manuscript. K.B. performed cell culture for virus amplification. L.T., K.B, J.V and M.B worked in BSL-3 laboratory to concentrate and titrate the virus for assays. LF produced and purified the recombinant Spike protein. All ELISA, Western blots, CRP purification and BLITZ assays were performed by JV. All authors checked manuscript.

Corresponding author

Correspondence to Mangesh Bhide.

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Work with SARS-CoV-2 was performed in BSL-3 biocontainment laboratory.

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Víglaský, J., Bhide, K., Talpasova, L. et al. SARS-CoV-2 nucleocapsid protein forms complexes with soluble complement regulatory proteins that can bind to the virion. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37866-4

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  • Received: 11 July 2025

  • Accepted: 27 January 2026

  • Published: 29 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-37866-4

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Keywords

  • SARS-CoV-2
  • Complement regulatory proteins
  • Nucleocapsid protein
  • Spike protein
  • Complement system evasion
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