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ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells

By Xinyi Yang, Yuqi Zhu, Xiaying Zhao, Jun Liu, Jingna Xun, Songhua Yuan, Jun Chen, Hanyu Pan, Jinlong Yang, Jing Wang, Zhimin Liang, Xiaoting Shen, Yue Liang, Qinru Lin, Huitong Liang, Min Li, Hongzhou Lu, Huanzhang Zhu

Posted 18 Jan 2022
bioRxiv DOI: 10.1101/2022.01.15.476426

Currently, the COVID-19 pandemic, caused by SARS-CoV-2 infection, represents a serious public health problem worldwide. Although it has been shown that ACE2 serves as the main receptor for SARS-CoV-2 entry into host cells, studies have shown that ACE2 is expressed at extremely low levels in various tissues, especially in some organs where virus particles have been found, such as the heart and liver. Therefore, these organs potentially express additional SARS-CoV-2 receptors that have not yet been discovered. Here, by a genome-wide CRISPR-Cas9 activation library screening, we found that ASGR1 promoted SARS-CoV-2 infection of 293T cells. In Huh-7 and HepG2 cell lines, simultaneous knock out of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary liver parenchymal cells, both of which hardly express ACE2, SARS-CoV-2 could successfully establish an infection. After treatment with ASGR1 antibody, the infection rate significantly reduced. This suggests that SARS-CoV-2 infects liver cells mainly through an ASGR1-dependent mechanism. Finally, we also found that the soluble ASGR1 could not only prevent the SARS-CoV-2 pseudovirus, which binds to the ASGR1 receptors, from infecting host liver cells, but also had a protective effect on those expressing ACE2, indicating that administration of soluble ASGR1 protein may represent a new treatment approach. CONCLUSIONS: Colletively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells.

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