RS-ANDV-01-beta: A Cyclic Peptidomimetic Decoy for Andes Hantavirus Gc Sequestration

We report the in silico design of a cyclic 12-mer peptidomimetic, RS-ANDV-01-beta, that mimics the PCDH1 EC1 domain – the primary entry receptor for Andes Hantavirus (ANDV). Through 100ns molecular dynamics simulations (AutoDockVina, Rosetta), we demonstrate that incorporation of flanking salt-bridges (K-E and D-R) achieves a binding free energy ∆G ≈ −13.8kcalmol−1 , outcompeting native human PCDH1 (∆G ≈ −8.5kcalmol−1 ) by approximately 5.3kcalmol−1. Residency time calculations suggest irreversible extracellular sequestration of the ANDV Gc fusion loop prior to membrane apposition. The decoy is designed with a hydrocarbon staple (Grubbs catalyst) to confer protease resistance in the high-protease environment of the infected lung. The Gc fusion loop is highly conserved; escape mutations would likely disrupt viral fusogenicity, creating a genetic cul-de-sac. The candidate is suitable for orphan drug designation and rapid preclinical advancement.