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Synthetic Antibodies neutralize SARS-CoV-2 infection of mammalian cells

Shane Miersch, Mart Ustav Jr., Zhijie Li, James B. Case, Safder Ganaie, Giulia Matusali, Francesca Colavita, Daniele Lapa, Maria R. Capobianchi, View ORCID ProfileGuiseppe Novelli, Jang B. Gupta, Suresh Jain, Pier Paolo Pandolfi, Michael S. Diamond, Gaya Amarasinghe, James M. Rini, Sachdev S. Sidhu
doi: https://doi.org/10.1101/2020.06.05.137349
Shane Miersch
1Department of Molecular Genetics, Donnelly Centre, University of Toronto, Toronto, Ontario, M5S 3E1, Canada
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Mart Ustav Jr.
1Department of Molecular Genetics, Donnelly Centre, University of Toronto, Toronto, Ontario, M5S 3E1, Canada
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Zhijie Li
10Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5G 1M1
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James B. Case
2Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
3Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
4Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Safder Ganaie
3Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
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Giulia Matusali
6Laboratory of Virology, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
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Francesca Colavita
6Laboratory of Virology, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
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Daniele Lapa
6Laboratory of Virology, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
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Maria R. Capobianchi
6Laboratory of Virology, National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy
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Guiseppe Novelli
7Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy
8IRCCS Neuromed, Pozzilli (IS), Italy
9Department of Pharmacology, School of Medicine, University of Nevada, Reno, NV 89557, USA
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  • ORCID record for Guiseppe Novelli
Jang B. Gupta
12Intonation Research Laboratories, Hyderabad, India
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Suresh Jain
12Intonation Research Laboratories, Hyderabad, India
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Pier Paolo Pandolfi
13Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Italy
14DRI, Renown Health, Nevada System of Higher Education, Reno, NV 89557, USA
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Michael S. Diamond
2Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
3Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
4Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Gaya Amarasinghe
3Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
4Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
5Department of Biochemistry & Molecular Biophysics and Washington University School of Medicine, St. Louis, MO, USA
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James M. Rini
10Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5G 1M1
11Department of Biochemistry, University of Toronto, Toronto, Ontario, M5G 1M1
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Sachdev S. Sidhu
1Department of Molecular Genetics, Donnelly Centre, University of Toronto, Toronto, Ontario, M5S 3E1, Canada
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  • For correspondence: sachdev.sidhu@utoronto.ca
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ABSTRACT

Coronaviruses (CoV) are a large family of enveloped, RNA viruses that circulate in mammals and birds but have crossed the species barrier to infect humans seven times. Of these, three pathogenic strains have caused zoonotic infections in humans that result in severe respiratory syndromes including the Middle East Respiratory Syndrome (MERS-CoV), severe acute respiratory syndrome (SARS-CoV), and now SARS-CoV-2 coronaviruses, the latter of which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Here, we describe a panel of synthetic monoclonal antibodies, built on a human framework, that bind SARS-CoV-2 spike protein, compete for binding with ACE2, and potently inhibit infection by SARS-CoV-2. These antibodies were found to have a range of neutralization potencies against live virus infection in Vero E6 cells, potently inhibiting authentic SARS-CoV-2 virus at sub-nanomolar concentrations. These antibodies represent strong immunotherapeutic candidates for treatment of COVID-19.

Competing Interest Statement

S.S, P.P.P and S.J, are cofounders of Virna Therapeutics. The company is developing novel therapies for COVID-19 and other viruses.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted June 06, 2020.
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Synthetic Antibodies neutralize SARS-CoV-2 infection of mammalian cells
Shane Miersch, Mart Ustav Jr., Zhijie Li, James B. Case, Safder Ganaie, Giulia Matusali, Francesca Colavita, Daniele Lapa, Maria R. Capobianchi, Guiseppe Novelli, Jang B. Gupta, Suresh Jain, Pier Paolo Pandolfi, Michael S. Diamond, Gaya Amarasinghe, James M. Rini, Sachdev S. Sidhu
bioRxiv 2020.06.05.137349; doi: https://doi.org/10.1101/2020.06.05.137349
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Synthetic Antibodies neutralize SARS-CoV-2 infection of mammalian cells
Shane Miersch, Mart Ustav Jr., Zhijie Li, James B. Case, Safder Ganaie, Giulia Matusali, Francesca Colavita, Daniele Lapa, Maria R. Capobianchi, Guiseppe Novelli, Jang B. Gupta, Suresh Jain, Pier Paolo Pandolfi, Michael S. Diamond, Gaya Amarasinghe, James M. Rini, Sachdev S. Sidhu
bioRxiv 2020.06.05.137349; doi: https://doi.org/10.1101/2020.06.05.137349

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