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Host and viral determinants for efficient SARS-CoV-2 infection of the human lung

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-020-20457-w

2041-1723

Hin Chu, Bingjie Hu, Xiner Huang, Yue Chai, Dongyan Zhou, Yixin Wang, Huiping Shuai, Dong Yang, Yuxin Hou, Xi Zhang, Terrence Tsz‐Tai Yuen, Jian‐Piao Cai, Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Kelvin Kai‐Wang To, Ivy Hau-Yee Chan, Ko‐Yung Sit, CC Foo, Yhi Wong, Ada Tsui‐Lin Ng, Tan To Cheung, Simon Law, Wing‐Kuk Au, Melinda A. Brindley, Zhiwei Chen, Kin‐Hang Kok, Jasper Fuk‐Woo Chan, Kwok‐Yung Yuen,

COVID-19 diagnosis using AI

Abstract Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.