The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells

Abstract

The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, 24 and its rapid national and international spread pose a global health emergency. 25Coronaviruses use their spike proteins to select and enter target cells and insights into 26 nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and 27 reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-28 coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-29 S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. 30 Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-31 S-driven entry. Our results reveal important commonalities between 2019-nCoV and 32 SARS-coronavirus infection, which might translate into similar transmissibility and disease 33 pathogenesis. Moreover, they identify a target for antiviral intervention.34 35 One sentence summary: The novel 2019 coronavirus and the SARS-coronavirus share central 36 biological properties which can guide risk assessment and intervention. 37 38 39 40 41 42 43 44 45 46 author/funder. All rights reserved. No reuse allowed without permission.

The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China

“…In similar fashion to SARS-CoV, SARS-CoV-2 also uses ACE2 to gain entry into host cells. Hoffmann et al found that the cellular protease MPRSS2 blocks entry by cleaving the spike protein and may constitute a treatment option [118]. Zhou et al also confirmed that SARS-CoV-2 is able to use all but mouse ACE2 as an entry receptor for ACE2-expressing cells, but not cells without ACE2, indicating that the cell receptor for SARS-CoV-2 could be ACE2, and not other coronavirus receptors such as aminopeptidase N and dipeptidyl peptidase 4 [94].…”

Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence

“…The genome sequence homology of SARS-CoV-2 and SARS is about 79%, the 2019-nCoV is closer to the SARS-like bat CoVs (MG772933) than the SARS-CoV [7], which is descended from SARS-like bat CoVs. Interestingly, for high similarity of receptor-binding domain (RBD) in Spike-protein, several analyses reveal that SARS-CoV-2 uses angiotension-converting enzyme 2 (ACE2) as receptor, just like as SARS-CoV [8]. Coronavirus mainly recognizes the corresponding receptor on the target cell through the S protein on its surface and enters into the cell, then causing the occurrence of infection.…”

COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives

“…Cathepsins, ubiquitous lysosomal enzymes with a rather broad substrate specificity, cleave S during virus entry [66]. For 2019-nCoV, it was shown that TMPRSS 2 primes S, the cathepsins B and L are only required in the absence of this protease [67]. Interestingly, S of 2019-nCoV has acquired a polybasic motif at the S1/S2 boundary, which is not present in S of the bat CoVs and SARS-CoV [68].…”