A study found that alphacoronaviruses, which are mostly found in bats, may be able to penetrate human cells by using a previously unknown pathway.
An international team led by the United Kingdom's Five Lives Research Institute published the findings on Apr. 23 in the journal Nature.
About 60% to 75% of infectious diseases in humans are estimated to have originated in animals. This phenomenon, in which pathogens move from animals to humans, is called "zoonosis." Since the coronavirus disease (COVID-19) pandemic, interest has grown in which animal viruses can enter human cells and cause infection.
For a virus to enter a cell, it must match a specific protein on the cell surface, called a "receptor." This is often compared to a key-and-lock relationship. If the spike protein on the virus surface is the key, the human cell receptor is the lock. About six receptors used by coronaviruses have been identified so far, but research has focused mainly on betacoronaviruses such as SARS-CoV-2, which causes COVID-19, and the Middle East respiratory syndrome coronavirus (MERS-CoV). In contrast, there has been a relatively large research gap on alphacoronaviruses, which are widely spread in bats.
To fill this gap, the researchers selected 40 spike proteins representing the genetic diversity of alphacoronaviruses and attached them to pseudoviruses engineered not to cause actual disease for experiments.
As a result, most bat-derived alphacoronaviruses could not use the coronavirus receptors known to date. However, a coronavirus first isolated from the heart-nosed bat in Kenya (CcCoV-KY43) was able to enter human cells independently of known receptors.
Further analysis confirmed that this virus uses the human cell surface protein CEACAM6 as a new entry point. Related pseudoviruses found in Africa and some Eurasian lineages showed similar properties.
However, this study does not mean that alphacoronaviruses will immediately infect humans. When the researchers examined blood samples from 368 residents near bat-collection sites, they found no evidence that this virus was widespread among people. In other words, for now, the likelihood of easy human-to-human transmission appears low.
Kim Ho-jun, a senior researcher at the Korea Institute of Science and Technology (KIST) Biomedical Convergence Research Division, said, "Cell entry is a necessary condition for zoonosis, not a sufficient one," adding, "Efficient replication, immune evasion, and appropriate exposure routes are additional requirements for actual transmission."
The researchers said, "This study shows that lesser-known alphacoronaviruses can also open the door to human cells," adding, "New pathways for binding to human cells may emerge even among virus groups that have not yet drawn attention. Based on these findings, we may be able to detect and prepare for animal viruses' potential to infect humans at an earlier stage."
References
Nature (2026), DOI: https://doi.org/10.1038/s41586-026-10394-x