Graphical AbstractHighlights d SARS-CoV-2 uses the SARS-CoV receptor ACE2 for host cell entry d The spike protein of SARS-CoV-2 is primed by TMPRSS2 d Antibodies against SARS-CoV spike may offer some protection against SARS-CoV-2

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Highlights d B.1.1.7, B.1.351, and P.1 do not show augmented host cell entry d Entry inhibitors under clinical evaluation block all variants d B.1.351 and P.1 can escape from therapeutic antibodies d B.1.351 and P.1 evade antibodies induced by infection and vaccination

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 rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

No abstract

SUMMARYThe rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.