Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells
In Vitro studying identifying 35 compounds that inhibit SARS-CoV-2 in Vero cells and hepatocytes when treated prior to infection, and several compounds that slow replication when treated after infection: vitamin D, amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, and panobinosta. Authors use a nano-luciferase tagged version of the virus to quantify viral load.
2 In Vitro studies support the efficacy of vitamin D
[Mok, Pickard].
Pickard et al., 9 Sep 2021, peer-reviewed, 7 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: PLOS PATHOGENS
RESEARCH ARTICLE
Discovery of re-purposed drugs that slow
SARS-CoV-2 replication in human cells
Adam Pickard ID1,2*, Ben C. Calverley ID1,2, Joan Chang ID1,2, Richa Garva ID1,2, Sara Gago2,
Yinhui Lu1,2, Karl E. Kadler ID1,2*
1 Wellcome Centre for Cell-Matrix Research, University of Manchester, Oxford Road, Manchester, United
Kingdom, 2 School of Biological Sciences, Faculty of Biology, Medicine & Health, University of Manchester,
Manchester Academic Health Science Centre, Manchester, United Kingdom
* adam.pickard@manchester.ac.uk (AP); karl.kadler@manchester.ac.uk (KEK)
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OPEN ACCESS
Citation: Pickard A, Calverley BC, Chang J, Garva
R, Gago S, Lu Y, et al. (2021) Discovery of repurposed drugs that slow SARS-CoV-2 replication
in human cells. PLoS Pathog 17(9): e1009840.
https://doi.org/10.1371/journal.ppat.1009840
Editor: Andrew Pekosz, Johns Hopkins University
Bloomberg School of Public Health, UNITED
STATES
Received: May 27, 2021
Accepted: July 26, 2021
Published: September 9, 2021
Peer Review History: PLOS recognizes the
benefits of transparency in the peer review
process; therefore, we enable the publication of
all of the content of peer review and author
responses alongside final, published articles. The
editorial history of this article is available here:
https://doi.org/10.1371/journal.ppat.1009840
Copyright: © 2021 Pickard et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: All relevant data are
within the manuscript and its Supporting
Information files.
Abstract
COVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that
appear to be largely successful in stopping infection. However, therapeutics that can help
manage the disease are still required until immunity has been achieved globally. The identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in
stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARSCoV-2-ΔOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for
their ability to be infected and support replication of the virus, and performed a screen of
1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were
particularly effective in supporting SARS-CoV-2 replication, which is in-line with reported
proteinuria and liver damage in patients with COVID-19. Using the nano-luciferase as a
measure of virus replication we identified 35 drugs that reduced replication in Vero cells and
human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine,
atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3
to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected
cells. In conclusion, our study has identified strong candidates for drug repurposing, which
could prove powerful additions to the treatment of COVID.
Author summary
The identification of repurposed drugs that stop SARS-CoV-2 replication could have
enormous utility in stemming COVID-19. Here, using a nano-luciferase tagged version of
the virus (SARS-CoV-2-ΔOrf7a-NLuc) to quantitate viral load, we evaluated a range of
human cell types for their..
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