Abstract

Abstract The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention. One sentence summary The novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.

Keywords

CoronavirusTMPRSS2VirologyPandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)Severe acute respiratory syndrome coronavirusBetacoronavirusViral entryProteaseBiologyImmunologyMedicineVirusDiseaseInfectious disease (medical specialty)Viral replicationEnzymePathology

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Year
2020
Type
preprint
Citations
754
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Markus Hoffmann, Hannah Kleine‐Weber, Nadine Krüger et al. (2020). The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv (Cold Spring Harbor Laboratory) . https://doi.org/10.1101/2020.01.31.929042

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DOI
10.1101/2020.01.31.929042