| Literature DB >> 32972994 |
M Alejandra Tortorici1,2, Martina Beltramello3, Florian A Lempp4, Dora Pinto3, Ha V Dang1, Laura E Rosen4, Matthew McCallum1, John Bowen1, Andrea Minola3, Stefano Jaconi3, Fabrizia Zatta3, Anna De Marco3, Barbara Guarino3, Siro Bianchi3, Elvin J Lauron4, Heather Tucker4, Jiayi Zhou4, Alessia Peter3, Colin Havenar-Daughton4, Jason A Wojcechowskyj4, James Brett Case5, Rita E Chen5, Hannah Kaiser4, Martin Montiel-Ruiz4, Marcel Meury4, Nadine Czudnochowski4, Roberto Spreafico4, Josh Dillen4, Cindy Ng4, Nicole Sprugasci3, Katja Culap3, Fabio Benigni3, Rana Abdelnabi6, Shi-Yan Caroline Foo6, Michael A Schmid3, Elisabetta Cameroni3, Agostino Riva7, Arianna Gabrieli7, Massimo Galli7, Matteo S Pizzuto3, Johan Neyts6, Michael S Diamond5, Herbert W Virgin4,8,9, Gyorgy Snell4, Davide Corti3, Katja Fink10, David Veesler11.
Abstract
Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.Entities:
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Year: 2020 PMID： 32972994 PMCID： PMC7857395 DOI： 10.1126/science.abe3354
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728