Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses

  1. Zhe Zhao
  2. Paul Tran
  3. Ning Li
  4. Li Ou
  5. Jaewon Song
  6. Michael Sibilo
  7. Mike Castro
  8. Ananda Chowdhury
  9. Jennifer A. Bohl
  10. Jason M. Wu
  11. Thythy T. Do
  12. Baoshan Zhang
  13. Jenny Zhao
  14. Anasuya C. Pal
  15. Clancy W. Mullan
  16. David R. Martinez
  17. Richard W. Pierce
  18. Alicen Spaulding
  19. Sanghyun Lee
  20. Yaroslav Tsybovsky
  21. Leonid Serebryannyy
  22. Daniel C. Douek
  23. Tongqing Zhou
  24. Craig B. Wilen
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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 Å cryo-electron microscopy structure reveals that Langya attachment glycoprotein engages EPCR through a site distinct from that of Nipah’s ephrin binding site. 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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    Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses https://www.biorxiv.org/content/10.64898/2026.11.01.763137v1

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    Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses https://www.biorxiv.org/content/10.64898/2026.11.01.763137v1

  4. Version published to 10.64898/2026.11.01.763137v1 on bioRxiv