Computational design of potent, broadly neutralizing anti-Nipah virus and Hendra virus miniproteins
- 1University of Washington
Abstract
The prototype members of the genus Henipavirus, Nipah virus (NiV) and Hendra virus (HeV), cause recurrent zoonotic spillovers with case fatality rates ranging from 40-90% in humans. Currently, there are no approved vaccines or therapeutics for use in humans. Neutralizing antibodies targeting the NiV/HeV F- or G-glycoproteins protect animals from lethal challenge and are a main correlate of protection. However, antibody-based formulations are expensive, typically requiring hospital admission for administration and cold-chain for storage and transportation. To address the lack of shelf-stable clinical countermeasures, we computationally designed thermostable miniproteins that cross-react with subnanomolar affinities with both NiV and HeV F and G glycoproteins and inhibit viral entry in vitro with potencies comparable to lead antibodies. Oligomerized forms of these miniproteins have enhanced potency relative to their monomeric building blocks and increase the barrier for emergence of escape mutants, establishing them as promising preclinical candidates against these deadly viruses.
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BibTeX
@misc{sims2026computational,
title = {{Computational design of potent, broadly neutralizing anti-Nipah virus and Hendra virus miniproteins}},
author = {J. N. Sims and R. Gen and K. Sprouse and Y.-J. Park and Z. Wang and M. Amaya and A. Jays and B. Larsen and C. Stewart and J. T. Brown and R. Ragotte and R. Ravichandran and G. Ruth and X. Li and D. Vafeados and J. D. Bloom and C. Broder and D. Veesler and D. Baker},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751546},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751546v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Computational design of potent, broadly neutralizing anti-Nipah virus and Hendra virus miniproteins
AU - J. N. Sims
AU - R. Gen
AU - K. Sprouse
AU - Y.-J. Park
AU - Z. Wang
AU - M. Amaya
AU - A. Jays
AU - B. Larsen
AU - C. Stewart
AU - J. T. Brown
AU - R. Ragotte
AU - R. Ravichandran
AU - G. Ruth
AU - X. Li
AU - D. Vafeados
AU - J. D. Bloom
AU - C. Broder
AU - D. Veesler
AU - D. Baker
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751546
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751546v1
AB - The prototype members of the genus Henipavirus, Nipah virus (NiV) and Hendra virus (HeV), cause recurrent zoonotic spillovers with case fatality rates ranging from 40-90% in humans. Currently, there are no approved vaccines or therapeutics for use in humans. Neutralizing antibodies targeting the NiV/HeV F- or G-glycoproteins protect animals from lethal challenge and are a main correlate of protection. However, antibody-based formulations are expensive, typically requiring hospital admission for administration and cold-chain for storage and transportation. To address the lack of shelf-stable clinical countermeasures, we computationally designed thermostable miniproteins that cross-react with subnanomolar affinities with both NiV and HeV F and G glycoproteins and inhibit viral entry in vitro with potencies comparable to lead antibodies. Oligomerized forms of these miniproteins have enhanced potency relative to their monomeric building blocks and increase the barrier for emergence of escape mutants, establishing them as promising preclinical candidates against these deadly viruses.
ER -