What does this research mean for the field?

The in silico designed cyclic peptidomimetic RS-ANDV-01-beta irreversibly sequesters the Andes Hantavirus Gc fusion loop with significantly higher binding affinity than the native human PCDH1 receptor. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim is to design a cyclic peptidomimetic that can effectively mimic a receptor and sequester Andes Hantavirus Gc.

May 17, 2026Open Access

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

Key Points

The aim is to design a cyclic peptidomimetic that can effectively mimic a receptor and sequester Andes Hantavirus Gc.
In silico design of a cyclic 12-mer peptidomimetic RS-ANDV-01-beta
Molecular dynamics simulations using AutoDockVina and Rosetta for binding affinity analysis
Incorporation of salt-bridges to enhance binding free energy and resistance to proteases
RS-ANDV-01-beta shows a binding free energy of ∆G ≈ −13.8 kcal/mol, outperforming human PCDH1 at ∆G ≈ −8.5 kcal/mol
Residency time calculations indicate irreversible sequestration of ANDV Gc prior to membrane fusion
Potential for rapid preclinical use and orphan drug designation due to promising results.

Abstract

Abstract 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.

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