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Updated: Jan 7, 2026

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Decoding the cross-immune pressure: Dengue's role in SARS-CoV-2 evolution.

Abinash Mallick1, Rudra Chhajer1, Subhajit Biswas1,2

  • 1Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, West Bengal 700032, India.

Computational and Structural Biotechnology Journal
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Dengue virus antibodies show cross-reactivity with SARS-CoV-2, influencing spike protein mutations. These dengue virus antibodies may exert selection pressure on SARS-CoV-2 evolution.

Keywords:
Cross-reactivityDengueEvolutionMutationsSARS-CoV-2Spike

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Area of Science:

  • Virology
  • Immunology
  • Structural Biology

Background:

  • Cross-reactivity between Dengue virus (DV) antibodies (Abs) and SARS-CoV-2 Abs has been observed, suggesting potential cross-protection.
  • Emergent SARS-CoV-2 variants exhibit mutations in the spike protein, potentially to evade interactions with DV Abs.
  • Understanding these interactions is crucial for comprehending viral evolution and immune responses in co-endemic regions.

Purpose of the Study:

  • To investigate the impact of cross-reactive DV Abs on SARS-CoV-2 spike protein mutations.
  • To analyze the structural basis of these cross-interactions using computational methods.
  • To assess the potential of DV Abs to exert selection pressure on SARS-CoV-2.

Main Methods:

  • Analysis of mutations in SARS-CoV-2 spike protein across major variants (e.g., Kent, Delta, Omicron).
  • Structural studies and molecular docking simulations using Dengue virus type 2 (DV-2) envelope (E) Abs.
  • Enzyme-Linked Immunosorbent Assay (ELISA) to detect cross-binding of pre-pandemic DV Ab-positive sera to SARS-CoV-2 spike Receptor-Binding Domain (RBD) peptides.
  • Surrogate virus neutralization tests to evaluate cross-neutralization potential.

Main Results:

  • Majority of signature mutations in SARS-CoV-2 spike variants appear predominantly influenced by DV Abs.
  • Specific cross-binding observed between pre-pandemic DV Ab-positive sera and wild-type SARS-CoV-2 RBD peptides.
  • Docking simulations revealed maximum cross-interactions between DV E Abs and specific RBD regions.
  • Cross-reactive DV Abs demonstrated cross-neutralization potential against SARS-CoV-2.
  • Later SARS-CoV-2 variants (Omicrons) showed significantly reduced cross-reactivity with DV compared to earlier strains.

Conclusions:

  • Dengue virus antibodies play a significant role in shaping SARS-CoV-2 spike protein mutations.
  • Cross-reactive DV Abs can exert selection pressure on SARS-CoV-2, influencing its evolutionary trajectory.
  • The observed reduction in cross-reactivity in recent variants suggests an ongoing evolutionary adaptation of SARS-CoV-2 to evade DV Ab-mediated pressure.