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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 ProfileGiuseppe 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
3Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
4Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Safder Ganaie
3Molecular 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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Giuseppe 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 Giuseppe 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
3Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
4Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Gaya Amarasinghe
3Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
4Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
5Biochemistry & 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. Three highly pathogenic strains have caused zoonotic infections in humans that result in severe respiratory syndromes including the Middle East Respiratory Syndrome CoV (MERS), Severe Acute Respiratory Syndrome CoV (SARS), and the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. Here, we describe a panel of synthetic monoclonal antibodies, built on a human IgG framework, that bind to the spike protein of SARS-CoV-2 (the causative agent of COVID-19), compete for ACE2 binding, and potently inhibit SARS-CoV-2. All antibodies that exhibited neutralization potencies at sub-nanomolar concentrations against SARS-CoV-2/USA/WA1 in Vero E6 cells, also bound to the receptor binding domain (RBD), suggesting competition for the host receptor ACE2. 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 10, 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, Giuseppe 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, Giuseppe 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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