Structural insights into an aptainhibitor of the SARS-CoV-2 E protein using molecular docking, molecular dynamics, and biophysical analyses.

Apt-E-36-3, a 30-mer DNA aptainhibitor, binds the SARS-CoV-2 E protein with nanomolar affinity and blocks its oligomerization, offering a potential therapeutic approach.

• Why it matters: Targeting the conserved E protein's oligomerization could reduce viral virulence and mitigate COVID-19 severity, addressing a critical need for variant-resistant treatments.
• What they did: Researchers used molecular dynamics simulations and surface plasmon resonance assays to characterize Apt-E-36-3's interactions with the E protein and its C-terminal domain, revealing binding affinities of 1.97 and 11.8 nM.
• The result: Apt-E-36-3 effectively inhibits E protein self-association by 50%, providing an atomic-level structural basis for designing therapeutics that specifically target conserved viral proteins.