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A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals

Laura Riva, Shuofeng Yuan, Xin Yin, Laura Martin-Sancho, Naoko Matsunaga, Sebastian Burgstaller-Muehlbacher, Lars Pache, Paul P. De Jesus, Mitchell V. Hull, Max Chang, Jasper Fuk-Woo Chan, Jianli Cao, Vincent Kwok-Man Poon, Kristina Herbert, Tu-Trinh Nguyen, Yuan Pu, Courtney Nguyen, Andrey Rubanov, Luis Martinez-Sobrido, Wen-Chun Liu, Lisa Miorin, Kris M. White, Jeffrey R. Johnson, Christopher Benner, Ren Sun, Peter G. Schultz, View ORCID ProfileAndrew Su, Adolfo Garcia-Sastre, Arnab K. Chatterjee, Kwok-Yung Yuen, Sumit K. Chanda
doi: https://doi.org/10.1101/2020.04.16.044016
Laura Riva
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Shuofeng Yuan
2State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
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Xin Yin
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Laura Martin-Sancho
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Naoko Matsunaga
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Sebastian Burgstaller-Muehlbacher
3Center for Integrative Bioinformatics Vienna, Max Perutz Laboratories, University of Vienna and Medical University of Vienna, Austria
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Lars Pache
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Paul P. De Jesus
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Mitchell V. Hull
4Calibr at Scripps Research, La Jolla, CA, 92037, USA
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Max Chang
5Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
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Jasper Fuk-Woo Chan
2State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
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Jianli Cao
2State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
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Vincent Kwok-Man Poon
2State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
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Kristina Herbert
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Tu-Trinh Nguyen
4Calibr at Scripps Research, La Jolla, CA, 92037, USA
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Yuan Pu
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Courtney Nguyen
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Andrey Rubanov
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Luis Martinez-Sobrido
6Texas Biomedical Research Institute, San Antonio, TX, USA
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Wen-Chun Liu
6Texas Biomedical Research Institute, San Antonio, TX, USA
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Lisa Miorin
7Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
8Global Health and Emerging pathogenes Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, US
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Kris M. White
7Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
8Global Health and Emerging pathogenes Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, US
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Jeffrey R. Johnson
7Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
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Christopher Benner
5Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
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Ren Sun
9Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA
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Peter G. Schultz
4Calibr at Scripps Research, La Jolla, CA, 92037, USA
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Andrew Su
10Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA
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  • ORCID record for Andrew Su
Adolfo Garcia-Sastre
7Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
8Global Health and Emerging pathogenes Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, US
11Department of Medicine - Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
12The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
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Arnab K. Chatterjee
4Calibr at Scripps Research, La Jolla, CA, 92037, USA
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  • For correspondence: schanda@sbpdiscovery.org achatterjee@scripps.edu kyyuen@hku.hk
Kwok-Yung Yuen
2State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
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  • For correspondence: schanda@sbpdiscovery.org achatterjee@scripps.edu kyyuen@hku.hk
Sumit K. Chanda
1Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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  • For correspondence: schanda@sbpdiscovery.org achatterjee@scripps.edu kyyuen@hku.hk
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Abstract

The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. As the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug registration of an antiviral is >10 years, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.

Competing Interest Statement

The authors have declared no competing interest.

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A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals
Laura Riva, Shuofeng Yuan, Xin Yin, Laura Martin-Sancho, Naoko Matsunaga, Sebastian Burgstaller-Muehlbacher, Lars Pache, Paul P. De Jesus, Mitchell V. Hull, Max Chang, Jasper Fuk-Woo Chan, Jianli Cao, Vincent Kwok-Man Poon, Kristina Herbert, Tu-Trinh Nguyen, Yuan Pu, Courtney Nguyen, Andrey Rubanov, Luis Martinez-Sobrido, Wen-Chun Liu, Lisa Miorin, Kris M. White, Jeffrey R. Johnson, Christopher Benner, Ren Sun, Peter G. Schultz, Andrew Su, Adolfo Garcia-Sastre, Arnab K. Chatterjee, Kwok-Yung Yuen, Sumit K. Chanda
bioRxiv 2020.04.16.044016; doi: https://doi.org/10.1101/2020.04.16.044016
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A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals
Laura Riva, Shuofeng Yuan, Xin Yin, Laura Martin-Sancho, Naoko Matsunaga, Sebastian Burgstaller-Muehlbacher, Lars Pache, Paul P. De Jesus, Mitchell V. Hull, Max Chang, Jasper Fuk-Woo Chan, Jianli Cao, Vincent Kwok-Man Poon, Kristina Herbert, Tu-Trinh Nguyen, Yuan Pu, Courtney Nguyen, Andrey Rubanov, Luis Martinez-Sobrido, Wen-Chun Liu, Lisa Miorin, Kris M. White, Jeffrey R. Johnson, Christopher Benner, Ren Sun, Peter G. Schultz, Andrew Su, Adolfo Garcia-Sastre, Arnab K. Chatterjee, Kwok-Yung Yuen, Sumit K. Chanda
bioRxiv 2020.04.16.044016; doi: https://doi.org/10.1101/2020.04.16.044016

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