TMPRSS2 as a Viral Entry Target

TMPRSS2 (Transmembrane Serine Protease 2) is a host serine protease involved in activation of viral Spike proteins during entry into host cells.

Because TMPRSS2 participates in viral entry mechanisms, it has become an important target for antiviral research.

Hesperidin Interaction with TMPRSS2

Computational docking studies identified Hesperidin as a strong TMPRSS2-interacting flavonoid.

LigPlot+ interaction mapping demonstrated interaction with catalytic residues:

  • His296
  • Asp345
  • Ser441

Hydrogen bond distances in the range of approximately 2.7-3.0 A supported stable interaction geometry.

Experimental TMPRSS2 Inhibition

Fluorescence-based TMPRSS2 inhibition assays demonstrated dose-dependent inhibition behavior for:

  • Hesperidin
  • Hesperetin
  • Rutin

Hesperetin demonstrated the strongest inhibitory profile among the tested flavonoids.

Calu-3 Validation System

Calu-3 human lung epithelial cells expressing TMPRSS2 were used to evaluate biological relevance.

Flavonoid pre-treatment partially reduced Spike-associated cellular toxicity under tested conditions.

Mechanistic Significance

The integrated computational and experimental data suggest that flavonoid interaction with TMPRSS2 may contribute to a broader multi-target antiviral framework.

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