Computational shielding of chikungunya viral prefusion with permeable cyclic-minipeptides
Abstract
Permeable cyclic-minipeptide-conformer candidates were computationally co-generated with the aim of shielding the protected prefusion-loops (FL) of the envelop E2E1 protein heterodimers of chikungunya virus (CHIKV). This work attempts to prevent some of the earliest pH-dependent dissociation E2E1 events which trigger CHIKV fusion/ infectivity by fully exposing their FL. To co-generate de novo candidates, a minimized prefusion CHIKV E2E1 (minE2E1) model including minimal E2-protective and E1-FL sequences was targeted by BoltzGen. The advantages of the cogenerated top-affinity nanoMolar candidates include higher affinities compared to previous neutralizing peptides, easier chemical synthesis, low antigenicity and strong conformer stabilities. Top-affinity parents were computationally mutated to derive thousands of membrane-permeable candidates conserving their cyclization, targets and affinities. A few membrane-permeable top-affinity candidates may serve for experimentally-guided validation of possible inhibition of CHIKV fusion and infection.
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BibTeX
@misc{coll2026computational,
title = {{Computational shielding of chikungunya viral prefusion with permeable cyclic-minipeptides}},
author = {Julio Coll},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009994/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009994/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Computational shielding of chikungunya viral prefusion with permeable cyclic-minipeptides
AU - Julio Coll
PY - 2026
DA - 2026/10/06
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009994/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009994/v1
AB - Permeable cyclic-minipeptide-conformer candidates were computationally co-generated with the aim of shielding the protected prefusion-loops (FL) of the envelop E2E1 protein heterodimers of chikungunya virus (CHIKV). This work attempts to prevent some of the earliest pH-dependent dissociation E2E1 events which trigger CHIKV fusion/ infectivity by fully exposing their FL. To co-generate de novo candidates, a minimized prefusion CHIKV E2E1 (minE2E1) model including minimal E2-protective and E1-FL sequences was targeted by BoltzGen. The advantages of the cogenerated top-affinity nanoMolar candidates include higher affinities compared to previous neutralizing peptides, easier chemical synthesis, low antigenicity and strong conformer stabilities. Top-affinity parents were computationally mutated to derive thousands of membrane-permeable candidates conserving their cyclization, targets and affinities. A few membrane-permeable top-affinity candidates may serve for experimentally-guided validation of possible inhibition of CHIKV fusion and infection.
ER -