A SARS-CoV-2 Neutralizing Antibody Selected from COVID-19 Patients by Phage Display is Binding to the ACE2-RBD Interface and is Tolerant to Known RBD Mutations

Bertoglio, Federico; Fühner, Viola; Ruschig, Maximilian; Heine, Philip Alexander; Rand, Ulfert; Klünemann, Thomas; Meier, Doris; Langreder, Nora; Steinke, Stephan; Ballmann, Rico; Schneider, Kai-Thomas; Roth, Kristian Danial Ralph; Kühn, Philipp; Riese, Peggy; Schäckermann, Dorina; Korn, Janin; Koch, Allan; Zock-Emmenthal, Susanne; Becker, Marlies; Scholz, M; Moreira, Gustavo Marçal Schmidt Garcia; Wenzel, Esther Veronika; Russo, Giulio; Garritsen, Hendrikus S.P.; Casu, Sebastian; Gerstner, Andreas O. H.; Roth, Günter; Hermann, Andreas; Schirrmann, Thomas; Dübel, Stefan; Frenzel, André; Heuvel, Joop van den; Čičin‐Šain, Luka; Schubert, Maren; Hust, Michael

doi:10.2139/ssrn.3754550

Cited by 7 publications

(1 citation statement)

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“…4C). Antibodies in Class 1-3 are SARS-CoV-2 speci c. Class 1, as represented by antibody CB6 5 , which targets a region with a large overlapping area to the RBM, comprises a total of 21 reported Abs 4,5,21,22,[30][31][32][33][34][35][36][37][38][39] . Class 2, represented by P2B-2F6 5 , which targets a reciprocal region that partially overlaps with the RBM, includes a total of 19 Abs 4,30,37,38,[40][41][42][43][44][45][46][47] .…”

Section: Mutation Resistance Of 7d6/6d6 and Classi Cation Of Sars-cov-2 Rbd Nabsmentioning

confidence: 99%

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist to circulating variants

Xue

Zheng

et al. 2021

Preprint

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The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the still ravaging COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Significantly, both antibodies confer good mutation resistance to the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics, and can also inform the design of pan-sarbecovirus vaccines.

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Section: Mutation Resistance Of 7d6/6d6 and Classi Cation Of Sars-cov-2 Rbd Nabsmentioning

confidence: 99%

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist to circulating variants

Xue

Zheng

et al. 2021

Preprint

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COR-101, ein menschlicher Antikörper gegen COVID-19

Dübel

Herrmann²,

Schirrmann³

et al. 2021

Biospektrum

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COR-101 is a fully human, Fc silenced IgG that was discovered by antibody phage display. It reduced the SARS-CoV-2 virus load in the lung by more than 99 percent in Hamster models and led to much faster recovery. Its mode of action has been elucidated by solving the atomic structure of its interaction with SARS-CoV-2. The antibody competes with ACE2 binding by blocking a large area of the SARS-CoV-2 spike protein.

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The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study

Fratev

2020

Preprint

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The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased; about over 100 times. The K417N mutation had much more pronounced effect and in a combination with N501Y fully abolished the antibody effect. This may explain the observed in UK and South Africa more spread of the virus but also raise an important question about the possible human immune response and the success of already available vaccines.

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A SARS-CoV-2 Neutralizing Antibody Selected from COVID-19 Patients by Phage Display is Binding to the ACE2-RBD Interface and is Tolerant to Known RBD Mutations

Cited by 7 publications

References 0 publications

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist to circulating variants

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist to circulating variants

COR-101, ein menschlicher Antikörper gegen COVID-19

The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study

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