SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Abstract: The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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Cites background from "SARS-CoV-2 Cell Entry Depends on AC..."
...The low rate of infection in A549 cells is postulated to be the result of low expression of the viral receptor ACE2 (Harcourt et al., 2020; Hoffmann et al., 2020)....
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References
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"SARS-CoV-2 Cell Entry Depends on AC..." refers background in this paper
...Infections were also detected in 24 countries outside China and were associated with international travel....
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...Subsequently, human-to-human transmission occurred (Chan et al., 2020) and the disease, now termed coronavirus disease 19 (COVID-19) rapidly spread within China....
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...On February 12, 2020, a total of 44,730 laboratoryconfirmed infections were reported in China, including 8,204 Cell 181, 271–280, April 16, 2020 ª 2020 Elsevier Inc. 271 (A) Schematic illustration of SARS-S including functional domains (RBD, receptor binding domain; RBM, receptor bindingmotif; TD, transmembrane domain) and proteolytic cleavage sites (S1/S2, S20 )....
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...The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency....
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...In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China (Huang et al., 2020; Wang et al., 2020; Zhu et al., 2020)....
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15,285 citations
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"SARS-CoV-2 Cell Entry Depends on AC..." refers background in this paper
...Subsequently, human-to-human transmission occurred (Chan et al., 2020) and the disease, now termed coronavirus disease 19 (COVID-19) rapidly spread within China....
[...]