Infectivity, pathogenicity, and immune protection of the pangolin-origin SARS-CoV-2 related coronavirus

The natural host of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) to human remains largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of pCoV-GD01, the most closest pCoV to SARS-CoV-2, in human cells, human tracheal epithelium organoids, and established animal models in comparision with. The results show that pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice, and could establish efficient transmission among co-caged hamsters. Interestingly, in-depth antigenic analysis and animal heterologous challenge experiments demonstrate that pre-existing immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide cross-protection against pCoV-GD01 challenge. These collective results highlight the potential risk of persistent spillover from animal hosts like the pangolin, and the COVID-19 pandemic and massive vaccination have reduced the possibility of pCoVs circulation in mankind. Overall design: Human airway epithelium primary cells were induced to generate 2D airway organoids. Then, SARS-CoV-2 and pCoV-GD01 used to infect the organoids. Samples were harvested for transcriptome sequencing.