A subset of bat alphacoronaviruses (a major group of coronaviruses) are found to have the potential to enter human cells by exploiting a previously unknown cellular gateway, according to a study published in Nature. Although no strong evidence of infection have been detected in humans to date, the findings may broaden how scientists assess pandemic risk in the largely understudied alphacoronavirus group.
An estimated 60–75% of human infectious diseases originate in animals, making zoonotic transmission a central concern for global health. In the aftermath of the COVID‑19 pandemic, attention has focused on understanding whether animal viruses infect human cells. For coronaviruses, this process depends on interactions between the viral spike protein and host cell receptors. Although six such receptors have been identified, most knowledge comes from betacoronaviruses, such as SARS‑CoV‑2 and MERS‑CoV. By contrast, alphacoronaviruses, a highly diverse group that circulates predominantly in bats, remain poorly understood.
To tackle this gap, Giulia Gallo and colleagues used a computational approach to select a representative panel of 40 spike proteins representing much of the known genetic diversity of alphacoronaviruses. These spikes were incorporated into lab‑safe pseudoviruses and tested against libraries of known coronavirus receptors from different species. The majority of bat‑derived alphacoronavirus spike proteins could not use any previously identified receptors. However, one virus spike protein, from the Cardioderma cor coronavirus (originally isolated from heart-nosed bats in Kenya), could enter human cells independently of known receptors. A large‑scale screen of human cell‑surface proteins identified CEACAM6 as the entry receptor, a finding confirmed by structural and functional analyses. Related viruses from Africa, and, to a lesser extent, Eurasia, showed similar receptor usage.
Blood samples from people living near the bat‑sampling sites showed no evidence of widespread infection, suggesting that spillover remains unlikely. Nonetheless, the study demonstrates that alphacoronaviruses can engage human‑expressed receptors and provides a blueprint for identifying potential zoonotic spillover events before they emerge.
Article details
Heart-nosed bat alphacoronaviruses use human CEACAM6 to enter cells
Corresponding Author:
Dalan Bailey
The Pirbright Institute
Woking, UK
Email: [email protected]
News & Views corresponding author:
Huan Yan
Wuhan University
Wuhan, China
Email: [email protected]
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