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      SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies

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          Abstract

          The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, the recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa) and P.1 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of all variants into human cells is susceptible to blockade by the entry inhibitors soluble ACE2, Camostat, EK-1 and EK-1-C4. In contrast, entry of the B.1.351 and P.1 variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment. Moreover, entry of these variants was less efficiently inhibited by plasma from convalescent COVID-19 patients and sera from BNT162b2 vaccinated individuals. These results suggest that SARS-CoV-2 may escape neutralizing antibody responses, which has important implications for efforts to contain the pandemic.

          Abstract

          Comparison of the SARS-CoV-2 variants B.1.1.7, B.1.351 and P.1 show that inhibitors under clinical evaluation are still effective in blocking entry though the B.1.351 and P.1 variants evade antibody responses induced upon infection as well as vaccination and evade certain therapeutic antibodies.

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          Most cited references52

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary 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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              Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

              Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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                Author and article information

                Journal
                Cell
                Cell
                Cell
                Elsevier Inc.
                0092-8674
                1097-4172
                20 March 2021
                20 March 2021
                Affiliations
                [1 ]Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany
                [2 ]Faculty of Biology and Psychology, Georg-August-University Göttingen, Wilhelmsplatz 1, 37073 Göttingen, Germany
                [3 ]Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstr. 1, 89081 Ulm, Germany
                [4 ]Junior Research Group Herpesviruses - Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany
                [5 ]Department of Anaesthesiology, University of Göttingen Medical Center, Göttingen, Georg-August University of Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany
                [6 ]Division of Molecular Immunology, Department of Internal Medicine 3, Friedrich-Alexander University of Erlangen-Nürnberg, Glückstraße 6 , 91054 Erlangen , Germany
                [7 ]Department of Transfusion Medicine, Ulm University, Helmholtzstraße 10, 89081 Ulm, Germany
                [8 ]Institute for Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg – Hessen and University Hospital Ulm, Helmholtzstraße 10, 89081 Ulm, Germany
                [9 ]Department of Internal Medicine 1, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany
                [10 ]Core Facility Functional Peptidomics, Ulm University Medical Center, Meyerhofstr. 4, 89081 Ulm, Germany
                Author notes
                []Corresponding author
                [11]

                These authors contributed equally

                [12]

                Lead contact

                Article
                S0092-8674(21)00367-6
                10.1016/j.cell.2021.03.036
                7980144
                33794143
                7affd425-5608-4b49-9ad2-a346cbc31b34
                © 2021 Elsevier Inc.

                Since January 2020 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.

                History
                : 11 February 2021
                : 26 February 2021
                : 16 March 2021
                Categories
                Article

                Cell biology
                Cell biology

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