Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing

Laura Riva, Shuofeng Yuan, Xin Yin, Laura Martin-Sancho, Naoko Matsunaga, Lars Pache, Sebastian Burgstaller-Muehlbacher, Paul D. Jesus, Peter Teriete, Mitchell V. Hull, Max W. Chang, Jasper Fuk-Woo Chan, Jianli Cao, Vincent Kwok-Man Poon, Kristina M. Herbert, Kuoyuan Cheng, Tu-Trinh H. Nguyen, Andrey Rubanov, Yuan Pu, Courtney Nguyen, Angela Choi, Raveen Rathnasinghe, Michael Schotsaert, Lisa Miorin, Marion Dejosez, Thomas P. Zwaka, Ko-Yung Sit, Luis Martinez-Sobrido, Wen-Chun Liu, Kris M. White, Mackenzie E. Chapman, Emma K. Lendy, Richard J. Glynne, Randy Albrecht, Eytan Ruppin, Andrew D. Mesecar, Jeffrey R. Johnson, Christopher Benner, Ren Sun, Peter G. Schultz, Andrew I. Su, Adolfo García-Sastre, Arnab K. Chatterjee (), Kwok-Yung Yuen () and Sumit K. Chanda ()
Additional contact information
Laura Riva: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Shuofeng Yuan: The University of Hong Kong, Hong Kong Special Administrative Region
Xin Yin: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Laura Martin-Sancho: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Naoko Matsunaga: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Lars Pache: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Sebastian Burgstaller-Muehlbacher: University of Vienna and Medical University of Vienna
Paul D. Jesus: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Peter Teriete: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Mitchell V. Hull: Calibr at Scripps Research
Max W. Chang: University of California, San Diego
Jasper Fuk-Woo Chan: The University of Hong Kong, Hong Kong Special Administrative Region
Jianli Cao: The University of Hong Kong, Hong Kong Special Administrative Region
Vincent Kwok-Man Poon: The University of Hong Kong, Hong Kong Special Administrative Region
Kristina M. Herbert: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Kuoyuan Cheng: National Cancer Institute, National Institute of Health
Tu-Trinh H. Nguyen: Calibr at Scripps Research
Andrey Rubanov: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Yuan Pu: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Courtney Nguyen: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute
Angela Choi: Icahn School of Medicine at Mount Sinai
Raveen Rathnasinghe: Icahn School of Medicine at Mount Sinai
Michael Schotsaert: Icahn School of Medicine at Mount Sinai
Lisa Miorin: Icahn School of Medicine at Mount Sinai
Marion Dejosez: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai
Thomas P. Zwaka: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai
Ko-Yung Sit: The University of Hong Kong, Hong Kong Special Administrative Region
Luis Martinez-Sobrido: Texas Biomedical Research Institute
Wen-Chun Liu: Icahn School of Medicine at Mount Sinai
Kris M. White: Icahn School of Medicine at Mount Sinai
Mackenzie E. Chapman: Purdue University
Emma K. Lendy: Purdue University
Richard J. Glynne: Inception Therapeutics
Randy Albrecht: Icahn School of Medicine at Mount Sinai
Eytan Ruppin: National Cancer Institute, National Institute of Health
Andrew D. Mesecar: Purdue University
Jeffrey R. Johnson: Icahn School of Medicine at Mount Sinai
Christopher Benner: University of California, San Diego
Ren Sun: University of California
Peter G. Schultz: Calibr at Scripps Research
Andrew I. Su: The Scripps Research Institute
Adolfo García-Sastre: Icahn School of Medicine at Mount Sinai
Arnab K. Chatterjee: Calibr at Scripps Research
Kwok-Yung Yuen: The University of Hong Kong, Hong Kong Special Administrative Region
Sumit K. Chanda: Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute

Nature, 2020, vol. 586, issue 7827, 113-119

Abstract: Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)1. The development of a vaccine is likely to take at least 12–18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose–response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod2–4 and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from H9 human embryonic stem cell lines, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2577-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:586:y:2020:i:7827:d:10.1038_s41586-020-2577-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2577-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().