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February 19, 2026Peer Community JournalOpen Access

In silico evidence suggests that the SARS-CoV-2 Spike protein may target coiled-coil regions of numerous cytoskeletal and cytoskeleton-associated proteins

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Key result

In silico analysis indicates SARS-CoV-2 Spike protein preferentially targets coiled-coil regions of actin-binding and cytoskeletal proteins.

Why the study?

Understanding interactions between host and viral envelope proteins is essential to understand viral infection dynamics, specifically the mechanisms governing SARS-CoV-2 entry and intracellular trafficking.

Population

SARS-CoV-2-human protein-protein interactome dataset centered on the Spike S protein

Design

In silico reanalysis

Authors

PBPierre BrézellecCentre National de la Recherche Scientifique

Discussion

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Implication

No immediate clinical implications; hypothesis-generating for cytoskeletal roles in infection pending validation.

Key Points

  • The research aims to explore how SARS-CoV-2 Spike protein interacts with human cytoskeletal proteins.
  • Reanalyzed the SARS-CoV-2–human protein–protein interactome dataset.
  • Focused on the Spike S protein interactions with host proteins.
  • Investigated the prevalence of coiled-coil regions in actin-binding proteins and other cytoskeletal proteins.
  • Statistical overrepresentation of actin-binding proteins among Spike S interactors was observed.
  • The majority of partners contained a domain similar to Myosin II's C-terminal region.
  • Highlights a significant presence of coiled-coil regions in interactors related to the cytoskeleton.

Structured PICO

P
Population
In silico model analyzing 22 human protein interactors of the SARS-CoV-2 Spike S protein from a previously published protein-protein interactome dataset, and a subsequent set of 488 human proteins from the human proteome.
I
Intervention
In silico structural and functional analysis using Phyre2 and BackPhyre to identify shared domains (specifically the C-terminal region of Myosin II heavy chain) among Spike S interacting proteins.
O
Outcome
Statistical enrichment of cytoskeletal-associated proteins and identification of shared structural domains (coiled-coil regions similar to the C-terminal part of Myosin II heavy chain) among SARS-CoV-2 Spike S protein partners.

In silico analysis suggests that the SARS-CoV-2 Spike protein may interact with host cells by targeting coiled-coil regions prevalent in cytoskeletal proteins, potentially facilitating viral entry and intracellular trafficking.

Limitations

  • Relies on in silico evidence, direct biological extrapolations require caution
  • The critical interaction between the Spike S binding domain (RBD) and the host ACE2 was not identified in the original interactome dataset

Cite This Study

Pierre Brézellec (2026) studied this question. In silico analysis indicates SARS-CoV-2 Spike protein preferentially targets coiled-coil regions of actin-binding and cytoskeleton-associated proteins.

synapsesocial.com/papers/6996a8d4ecb39a600b3f0005https://doi.org/10.24072/pcjournal.681
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  5. 5An interaction between alpha-actinin and the beta 1 integrin subunit in vitro.1990 · 849 citations