Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses
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 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.
Authors
- Tongqing Zhou (ORCID: https://orcid.org/0000-0002-3935-4637)
- Daniel C. Douek (ORCID: https://orcid.org/0000-0001-5575-8634)
- Anasuya Chattopadhyay Pal (ORCID: https://orcid.org/0000-0002-0068-8912)
- Clancy W. Mullan (ORCID: https://orcid.org/0000-0002-2774-251X)
- Jennifer A. Bohl (ORCID: https://orcid.org/0000-0001-6057-1858)
- Mike Castro (ORCID: https://orcid.org/0000-0002-8045-1754)
- Leonid Serebryannyy (ORCID: https://orcid.org/0000-0003-0213-1779)
- Richard W. Pierce (ORCID: https://orcid.org/0000-0001-5941-8805)
- Yaroslav Tsybovsky (ORCID: https://orcid.org/0000-0002-2159-5248)
- Michael Q. Sibilo
- Craig B. Wilen (ORCID: https://orcid.org/0000-0003-2495-9403)
- Ning Li (ORCID: https://orcid.org/0000-0002-6518-2541)
- Zhe Zhao (ORCID: https://orcid.org/0000-0002-4119-0504)
- David R. Martinez (ORCID: https://orcid.org/0000-0002-1689-5529)
- Ananda Chowdhury
- Li Ou (ORCID: https://orcid.org/0000-0001-5653-8684)
- Baoshan Zhang
- Jaewon Song
- Thythy T. Do
- Sanghyun Lee
- Paul Tran
- Jenny Zhao
- Alicen Spaulding
- Jason M. Wu
Institutions
- Brown University (US)
- Yale University (US)
- Frederick National Laboratory for Cancer Research (US)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-02
- DOI
- https://doi.org/10.64898/2026.11.01.763137
- Primary Topic
- Virology and Viral Diseases
- Type
- preprint