Computational shielding of dengue viral prefusion with permeable cyclic-minipeptides
Abstract
Permeable cyclic-minipeptide-conformer candidates have been computationally cogenerated to shield the protected prefusionloops (FL) of dengue flavivirus (DENV). The objective was to prevent the pH-dependent dissociation events that trigger flavivirus fusion/ infectivity by exposing the FL highlyconserved sequences to homotrimer fusioncompetent conformations. For that, hundreds of BoltzGen candidates were co-generated targeting a prefusion minimized DENV envelope AB heterodimer (minEAB) model including both EA-protective and EB-FL sequences. The advantages of the newly cogenerated top-affinity nanoMolar candidates include possible bypassing of antibody-related enhancements, low antigenicity, easy chemical synthesis, and strong environmentalphysiological stability. Additionally, top-affinity parents were mutated to derive membranepermeable candidates conserving cyclization, minEAB targets and high-affinities. A few membrane-permeable candidates may serve for in vitro and animal-model experimentallyguided validations of inhibition of DENV fusion and infection.
Related
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BibTeX
@misc{coll2026computational,
title = {{Computational shielding of dengue viral prefusion with permeable cyclic-minipeptides}},
author = {Julio Coll},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008305/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008305/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Computational shielding of dengue viral prefusion with permeable cyclic-minipeptides
AU - Julio Coll
PY - 2026
DA - 2026/09/04
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008305/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008305/v1
AB - Permeable cyclic-minipeptide-conformer candidates have been computationally cogenerated to shield the protected prefusionloops (FL) of dengue flavivirus (DENV). The objective was to prevent the pH-dependent dissociation events that trigger flavivirus fusion/ infectivity by exposing the FL highlyconserved sequences to homotrimer fusioncompetent conformations. For that, hundreds of BoltzGen candidates were co-generated targeting a prefusion minimized DENV envelope AB heterodimer (minEAB) model including both EA-protective and EB-FL sequences. The advantages of the newly cogenerated top-affinity nanoMolar candidates include possible bypassing of antibody-related enhancements, low antigenicity, easy chemical synthesis, and strong environmentalphysiological stability. Additionally, top-affinity parents were mutated to derive membranepermeable candidates conserving cyclization, minEAB targets and high-affinities. A few membrane-permeable candidates may serve for in vitro and animal-model experimentallyguided validations of inhibition of DENV fusion and infection.
ER -