Viral Protein Functions and Host Interactions for Antiviral Drug Design

A new study found that SARS-CoV-2 nucleocapsid phosphorylation acts as a phosphorylation-dependent molecular switch, shifting the nucleocapsid from a genome‑packaging configuration into a dynamic RNA‑chaperone state. That reframing highlights kinase-substrate interfaces and phospho‑dependent RNA contacts as actionable antiviral targets.

Prior work emphasized the nucleocapsid's structural roles in condensation and virion assembly. New mechanistic mapping reframes the protein as a regulated, multifunctional hub: phosphorylation gates distinct biochemical modes. This shift reprioritizes specific posttranslational modification sites and host–virus interfaces for antiviral target validation and sets up the mechanistic detail that follows.

Core evidence derives from complementary biochemical and biophysical approaches, including phosphomimetic variants, mass photometry, and single‑molecule optical‑tweezer measurements.

The mechanistic map points to concrete drug‑discovery avenues — for example, targeting host kinases that modify the SRR, designing small molecules to disrupt phospho‑dependent RNA interfaces, or developing peptides or allosteric inhibitors that prevent phospho‑sensitive oligomerization. Each approach requires tiered biochemical and cell‑based screening followed by in vivo validation before prioritization for translational development.