NEW YORK – Scientists in China have discovered a new MERS-like bat coronavirus (CoV) in illegally smuggled Malayan pangolins that can infect and replicate in human cells, suggesting it may jump to humans someday and cause disease.
"Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence," Peng Zhou of the Wuhan Institute of Virology of the Chinese Academy of Sciences and colleagues wrote in a study published in Cell on Thursday.
Pangolins, they noted, are among the most trafficked game mammals and often come in contact with humans. Also, previous studies discovered coronavirus lineages related to SARS-CoV-2, the virus that caused the ongoing global pandemic, in pangolins smuggled from Malaysia to China, though it is still unclear how humans first became infected with SARS-CoV-2.
For their new study, the researchers screened 86 anal swab samples from Malayan pangolins that were illegally smuggled into China from Southeast Asia with a pan-CoV PCR test. Four of the samples were positive for coronavirus.
Next, they sequenced the positive samples and assembled four nearly identical full-length coronavirus genomes. Phylogenetic analysis showed that the new virus is a MERS-like coronavirus related to bat HKU4-CoV, and the researchers named it Manis javanica HKU4-related coronavirus (MjHKU4r-CoV).
Subsequent cell culture experiments showed that the new virus was able to infect human cells, using the human dipeptidyl peptidase-4 (hDPP4) receptor as its entry point. Moreover, the spike protein of the new virus has a furin cleavage site, enhancing its ability to infect human cells via human protease cleavage.
In addition, the virus was able to enter and replicate in human respiratory and intestinal organoids, suggesting that it can infect humans via this route. It could also infect hDDP4-transgenic mice intranasally and cause disease in the animals.
Next, the researchers tested three human-derived monoclonal antibodies that had shown strong activity against MERS-CoV as potential therapeutics against the new virus and found that none of them was effective. However, small molecule drugs such as remdesivir and EIDD-2801 showed antiviral activity against the virus.
One of the limitations of the study was that the researchers could not determine whether the new virus was spilled over directly from bats to pangolins, or whether there were other wild animals involved. They also did not test for any current spillover into humans but suggested that surveillance in humans is warranted, as the virus appears to be "potentially infectious and pathogenic to humans."
"Future surveillance is needed for a better understanding of the role of pangolins as a reservoir or susceptible host of bat-related CoVs, and for better preparation for the possible emergence of pangolin MERS-like CoV," the authors concluded.