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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
PubMed

Insights

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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