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Heart-nosed bat alphacoronaviruses use human CEACAM6 to enter cells
Giulia Gallo1,2, Antonello Di Nardo1, Doreen Lugano3
1The Pirbright Institute, Woking, UK.
Nature
|April 22, 2026
Summary
A bat coronavirus (CcCoV-KY43) can enter human cells using CEACAM6, a protein common in the lungs. This finding highlights potential zoonotic risks and the need for broader surveillance of alphacoronaviruses.
Area of Science:
- Virology
- Zoonotic Disease Research
- Structural Biology
Background:
- Identifying viruses with pandemic potential is crucial for global health security.
- Alphacoronaviruses are a diverse group, with some known to cause significant human illness.
- Understanding viral entry mechanisms is key to predicting and preventing zoonotic spillover.
Purpose of the Study:
- To computationally screen alphacoronavirus spike proteins for human cell entry.
- To identify novel receptors used by bat coronaviruses.
- To assess the zoonotic potential of Cardioderma cor coronavirus KY43 (CcCoV-KY43).
Main Methods:
- Computational selection of diverse alphacoronavirus spike proteins.
- Pseudotyped virus screening against human cell receptor libraries.
- Recombinant receptor-binding domain (RBD) interaction assays.
- Crystal structure determination of RBD-receptor complex.
- Serological immune surveillance in human populations.
Main Results:
- CcCoV-KY43 spike protein enabled human cell entry, utilizing human CEACAM proteins (CEACAM3, CEACAM5, CEACAM6).
- Human CEACAM6 overexpression conferred permissivity to human cells for CcCoV-KY43.
- Crystal structure revealed the CcCoV-KY43 RBD binds the IgV-like domain of human CEACAM6.
- Limited evidence of recent CcCoV-KY43 spillover in the Kenyan population studied.
- Related alphacoronaviruses from East Africa also utilize human CEACAM6.
Conclusions:
- Human CEACAM6 is a novel entry receptor for certain alphacoronaviruses, including CcCoV-KY43.
- Geographically widespread alphacoronaviruses use CEACAM6, suggesting broader zoonotic potential.
- East African alphacoronaviruses demonstrate a potential for human transmission via CEACAM6 utilization.
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