Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses
- 1Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale University School of Medicine, New
Abstract
Langya virus is a zoonotic parahenipavirus with pandemic potential that causes acute febrile illness in people. We identified endothelial protein C receptor (EPCR) as an entry receptor for Langya, Wenzhou, and Mojiang parahenipaviruses. A 3.1 [A] cryo-electron microscopy structure reveals that Langya attachment glycoprotein engages EPCR through a site distinct from that of the ephrin binding site of Nipah G. This binding mode resembles those of protein C and a malarial adhesin, demonstrating convergent evolution. Interface substitutions abolish entry, whereas natural variation explains differential human EPCR use and predicts receptor compatibility across 26 animal species. These findings establish EPCR as a receptor for the Langya clade and provide a structural framework for understanding cross-species transmission and human infection potential.
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BibTeX
@misc{zhao2026endothelial,
title = {{Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses}},
author = {Z. Zhao and P. Tran and N. Li and L. Ou and J. Song and M. Sibilo and M. Castro and A. Chowdhury and J. A. Bohl and J. M. Wu and T. T. Do and B. Zhang and J. Zhao and A. C. Pal and C. W. Mullan and D. R. Martinez and R. W. Pierce and A. Spaulding and S. Lee and Y. Tsybovsky and L. Serebryannyy and D. C. Douek and T. Zhou and C. B. Wilen},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.01.763137},
url = {https://www.biorxiv.org/content/10.64898/2026.11.01.763137v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses
AU - Z. Zhao
AU - P. Tran
AU - N. Li
AU - L. Ou
AU - J. Song
AU - M. Sibilo
AU - M. Castro
AU - A. Chowdhury
AU - J. A. Bohl
AU - J. M. Wu
AU - T. T. Do
AU - B. Zhang
AU - J. Zhao
AU - A. C. Pal
AU - C. W. Mullan
AU - D. R. Martinez
AU - R. W. Pierce
AU - A. Spaulding
AU - S. Lee
AU - Y. Tsybovsky
AU - L. Serebryannyy
AU - D. C. Douek
AU - T. Zhou
AU - C. B. Wilen
PY - 2026
DA - 2026/11/01
PB - bioRxiv
DO - 10.64898/2026.11.01.763137
UR - https://www.biorxiv.org/content/10.64898/2026.11.01.763137v1
AB - Langya virus is a zoonotic parahenipavirus with pandemic potential that causes acute febrile illness in people. We identified endothelial protein C receptor (EPCR) as an entry receptor for Langya, Wenzhou, and Mojiang parahenipaviruses. A 3.1 [A] cryo-electron microscopy structure reveals that Langya attachment glycoprotein engages EPCR through a site distinct from that of the ephrin binding site of Nipah G. This binding mode resembles those of protein C and a malarial adhesin, demonstrating convergent evolution. Interface substitutions abolish entry, whereas natural variation explains differential human EPCR use and predicts receptor compatibility across 26 animal species. These findings establish EPCR as a receptor for the Langya clade and provide a structural framework for understanding cross-species transmission and human infection potential.
ER -