Pangolin-derived sarbecoviruses show attenuated pathogenicity and transmissibility compared with SARS-CoV-2 in human ACE2 transgenic hamsters
6 affiliations
- 1The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Laboratory Clinical Base, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
- 2School of Public Health, Nanjing Medical University, Nanjing, China
- 3State Key Laboratory of Genetic Engineering, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
- 4School of Life Sciences, Inner Mongolia University, Hohhot, China
- 5State Key Laboratory of Reproductive Medicine and Offspring Health, Jiangsu Animal Experimental Center of Medicine and Pharmacy, Animal Core facility, Key Laboratory of Model Animal, Department of Cell Biology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China
- 6State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
Abstract
Genetic diversity of sarbecoviruses phylogenetically related to SARS-CoV-2 has been identified in Malayan pangolins. However, their potential pathogenicity and risk of cross-species transmission to humans remain largely unknown. In the present study, we performed comparative characterization of SARS-CoV-2 and two pangolin SARS-CoV-2-related viruses, named MpCoV-GD and MpCoV-GX, respectively, in human cell lines and organoids and human ACE2 (hACE2) transgenic hamsters. The cell-to-cell fusion assay showed that the Spike (S) protein of MpCoV-GD induces a stronger membrane fusion than the MpCoV-GX S protein, though weaker than the SARS-CoV-2 S protein. In human cells and organoids, both MpCoV-GX and MpCoV-GD replicated well but less efficiently than SARS-CoV-2. In K18-hACE2 hamsters, MpCoV-GD induced lung pathology comparable to SARS-CoV-2 by showing extensive damage to the alveolar parenchyma, while MpCoV-GX mainly caused alveolar wall thickening due to mild inflammatory cell infiltration. Similar to SARS-CoV-2, the two pangolin coronaviruses were capable of transmitting through direct contact and aerosol exposure, but their infectivity was largely attenuated during aerosol transmission. This study expands our understanding of the biological and infection features of the pangolin-derived sarbecoviruses. It demonstrates that current SARS-CoV-2-related therapeutics and pre-existing immunity can elicit cross-protection against the pangolin sarbecoviruses. Although their pathogenicity and transmissibility are relatively low, our findings suggest the necessity of continuing sarbecovirus surveillance in pangolins and other wildlife for prevention of future disease emergence.
IMPORTANCE: Pangolin-derived sarbecoviruses capable of infecting human cells underscore the role of wildlife as reservoirs for potential zoonotic emergence. MpCoV-GD induces lung pathology comparable to SARS-CoV-2 in hACE2 hamsters, highlighting the need for proactive assessment of novel coronaviruses. Although aerosol transmission of MpCoV-GD and MpCoV-GX is attenuated, their ability to spread via direct contact and airborne routes indicates a tangible risk of cross-species transmission. Importantly, cross-neutralizing activity or inhibition conferred by existing SARS-CoV-2 immunity and therapeutics suggests that current preparedness strategies may help mitigate their impact. These findings reinforce the necessity of sustained surveillance of sarbecoviruses in pangolins and other wildlife to enable early detection and prevention of future outbreaks with significant public health consequences.
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BibTeX
@article{lin2026pangolinderived,
title = {{Pangolin-derived sarbecoviruses show attenuated pathogenicity and transmissibility compared with SARS-CoV-2 in human ACE2 transgenic hamsters}},
author = {Hao-Feng Lin and Ren-Di Jiang and Li-Na Ji and Jin-Wei Zhang and Qian-Chun Gong and Hao-Rui Si and Yuan-Sen Shi and Xin-Hua Lin and Chen Qiu and Jian-Min Li and Mei-Qin Liu},
journal = {mBio},
year = {2026},
month = sep,
doi = {10.1128/mbio.01843-26},
url = {https://doi.org/10.1128/mbio.01843-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pangolin-derived sarbecoviruses show attenuated pathogenicity and transmissibility compared with SARS-CoV-2 in human ACE2 transgenic hamsters
AU - Hao-Feng Lin
AU - Ren-Di Jiang
AU - Li-Na Ji
AU - Jin-Wei Zhang
AU - Qian-Chun Gong
AU - Hao-Rui Si
AU - Yuan-Sen Shi
AU - Xin-Hua Lin
AU - Chen Qiu
AU - Jian-Min Li
AU - Mei-Qin Liu
PY - 2026
DA - 2026/09/24
JO - mBio
DO - 10.1128/mbio.01843-26
UR - https://doi.org/10.1128/mbio.01843-26
AB - Genetic diversity of sarbecoviruses phylogenetically related to SARS-CoV-2 has been identified in Malayan pangolins. However, their potential pathogenicity and risk of cross-species transmission to humans remain largely unknown. In the present study, we performed comparative characterization of SARS-CoV-2 and two pangolin SARS-CoV-2-related viruses, named MpCoV-GD and MpCoV-GX, respectively, in human cell lines and organoids and human ACE2 (hACE2) transgenic hamsters. The cell-to-cell fusion assay showed that the Spike (S) protein of MpCoV-GD induces a stronger membrane fusion than the MpCoV-GX S protein, though weaker than the SARS-CoV-2 S protein. In human cells and organoids, both MpCoV-GX and MpCoV-GD replicated well but less efficiently than SARS-CoV-2. In K18-hACE2 hamsters, MpCoV-GD induced lung pathology comparable to SARS-CoV-2 by showing extensive damage to the alveolar parenchyma, while MpCoV-GX mainly caused alveolar wall thickening due to mild inflammatory cell infiltration. Similar to SARS-CoV-2, the two pangolin coronaviruses were capable of transmitting through direct contact and aerosol exposure, but their infectivity was largely attenuated during aerosol transmission. This study expands our understanding of the biological and infection features of the pangolin-derived sarbecoviruses. It demonstrates that current SARS-CoV-2-related therapeutics and pre-existing immunity can elicit cross-protection against the pangolin sarbecoviruses. Although their pathogenicity and transmissibility are relatively low, our findings suggest the necessity of continuing sarbecovirus surveillance in pangolins and other wildlife for prevention of future disease emergence. IMPORTANCE: Pangolin-derived sarbecoviruses capable of infecting human cells underscore the role of wildlife as reservoirs for potential zoonotic emergence. MpCoV-GD induces lung pathology comparable to SARS-CoV-2 in hACE2 hamsters, highlighting the need for proactive assessment of novel coronaviruses. Although aerosol transmission of MpCoV-GD and MpCoV-GX is attenuated, their ability to spread via direct contact and airborne routes indicates a tangible risk of cross-species transmission. Importantly, cross-neutralizing activity or inhibition conferred by existing SARS-CoV-2 immunity and therapeutics suggests that current preparedness strategies may help mitigate their impact. These findings reinforce the necessity of sustained surveillance of sarbecoviruses in pangolins and other wildlife to enable early detection and prevention of future outbreaks with significant public health consequences.
SN - 2150-7511
ER -