Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Lulin Zhou; Zubiao Niu; Xiaoyi Jiang; Zhengrong Zhang; You Zheng; Zhongyi Wang; Yichao Zhu; Lihua Gao; Xiaoning Wang; Qiang Sun

The coronavirus is a large group of enveloped, single-strand positive-sense RNA viruses, with SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) the two known deadly viruses for human [10] . The spike (S) envelope glycoproteins on coronavirus are the major determinants of host cell entry. Proteolytic cleavage of S protein produces S1, the N-terminal region of S protein that is responsible for receptor binding, and S2, the trans-membrane C-terminal region of S protein that promotes membrane fusion. The cleavage step is often permissive for the fusion function of S protein as it helps to release the fusion peptide to insert into the target cellular membrane [10, 11] . Therefore, the host range and cell/tissue tropism of coronaviruses were believed to be controlled by the S protein engagement of host cell receptor, and by the proteolytic cleavage of the S protein as well [11] . Recently, works from several groups demonstrated, either bioinformatically or experimentally, that angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV virus [12] , is also a functional cellular receptor for SARS-CoV-2 virus [6, 7, [13] [14] [15] , and transmembrane protease serine 2 (TMPRSS2) and Furin are two proteases that process SARS-CoV-2 S protein to establish efficient infection [13, 14, 16, 17] .