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

By M. Hoffmann, Hannah Kleine-Weber, Nadine Krüger, Marcel Müller, Christian Drosten, S. Pöhlmann. bioRxiv, 2020

742 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases, Modeling and Simulation

View Paper: https://www.semanticscholar.org/paper/9f79913b17fa78cf9305693df76f832e1ada7bda

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The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. D. Veesler
2. A. Walls
3. M. A. Tortorici
4. Jun Zheng
5. Andrew T. McGuire
6. A. Wall
7. Young-Jun Park

In Modeling and Simulation

1. Jun Zheng

Citations in the corpus

• Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, result): “These results demonstrate hACE2 is a functional receptor for SARS-CoV-2, in agreement with recently reported Cell 180, 281–292, April 16, 2020 283 findings (Hoffmann et al., 2020; Letko et al., 2020; Zhou et al., 2020).”
• Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis (2020, positive): “The resultant increased systemic inflammation coupled with endothelial injury triggered by attachment of the virus to the angiotensin-2 receptor of the endothelial cells and viral replication leads to a prothrombotic endothelial dysfunction [53,54].”
• Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection (2020, background): “Liver damage was reported in SARS-infected patients [8].”
• Discovering drugs to treat coronavirus disease 2019 (COVID-19). (2020, background): “A TMPRSS2 inhibitor would block entry and thus constitute a treatment option (17).”
• Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies (2020, background): “It has been reported recently that SARS-CoV-2 is able to bind to the same receptor as SARS-CoV (ACE2) for cell entry, despite having multiple amino acid differences with SARS-CoV’s receptor-binding motif (Hoffmann et al., 2020; Letko & Munster, 2020; Lu et al., 2020; Zhou et al., 2020).”
• Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations (2020, background): “This allows proteolytic digestion by host cell proteases (TMPRSS2 and Furin) ultimately leading to internalization of the virion [32].”
• SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat (2020, result): “Similar to SARS-CoV, the entry of SARS-CoV-2 into host cells depends on the recognition and binding of S protein to ACE2 receptor of the host cells [14,33].”
• Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence (2020, positive): “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] .”
• COVID-19, ACE2, and the cardiovascular consequences (2020, background): “23) as a coreceptor to gain intracellular entry into the lungs and brain (17, 30, 52, 53, 62).”