Antibody from recovered SARS patient inhibits SARS-CoV-2 infectivity — proof of concept study

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An antibody isolated from a patient who has recovered from SARS (severe acute respiratory syndrome) is shown to effectively block SARS-CoV-2 infectivity. Antibodies that can neutralise the virus could help in the development of anti-viral treatments or vaccines.

Antibodies are produced by the immune system in response to foreign material invading the body. Monoclonal antibodies can target one specific protein (antigen) on a pathogen. Identifying monoclonal antibodies that can bind to the spike protein found on SARS-CoV-2 and SARS-related coronaviruses, which facilitates entry into human cells, may aid efforts to treat or prevent SARS-CoV-2 infection.

Davide Corti and colleagues at Humabs Biomed SA, University of Washington – Seattle, previously identified monoclonal antibodies, from a patient who recovered from SARS in 2003, that could inhibit SARS-related coronaviruses from both humans and animals. They investigated the potential for 25 of these antibodies to inhibit SARS-CoV-2 (an effect called cross-reactivity) and found eight antibodies that could bind to both the free virus and infected cells. One candidate, named S309, is shown to have particularly strong neutralising activity against SARS-CoV-2. By solving the crystal structure of S309, the authors demonstrate how the antibody binds to the viral spike protein. They show that S309 can act in combination with another, less potent, antibody that targets a different site on the spike protein of the virus. This synergistic activity could enhance neutralization while reducing the chance of resistant mutations emerging, the authors suggest.

The proof-of-concept findings suggest that cocktails of monoclonal antibodies may be worth exploring to control SARS-CoV-2. However, no experiments were performed in humans in this study.

Abstract
SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003.
One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

Authors
Dora Pinto, Young-Jun Park, Martina Beltramello, Alexandra C Walls, M Alejandra Tortorici, Siro Bianchi, Stefano Jaconi, Katja Culap, Fabrizia Zatta, Anna De Marco, Alessia Peter, Barbara Guarino, Roberto Spreafico, Elisabetta Cameroni, James Brett Case, Rita E Chen, Colin Havenar-Daughton, Gyorgy Snell, Amalio Telenti, Herbert W Virgin, Antonio Lanzavecchia, Michael S Diamond, Katja Fink, David Veesler Davide Corti

Nature abstract

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