Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Systematic Down-Selection of Repurposed Drug Candidates for COVID-19

Christopher A. MacRaild
ORCID logo ,
Muzaffar-Ur-Rehman Mohammed
ORCID logo ,
Faheem Faheem
ORCID logo ,
Sankaranarayanan Murugesan
ORCID logo ,
Ian K. Styles
,
Amanda L. Peterson
,
Carl M.J. Kirkpatrick
,
Matthew A. Cooper
,
Enzo A. Palombo
ORCID logo ,
Moana M. Simpson
,
Hardik Ashish Jain
ORCID logo ,
Vinti Agarwal
,
Alexander J. McAuley
ORCID logo ,
Anupama Kumar
* ,
Darren J. Creek
ORCID logo ,
Natalie L. Trevaskis
ORCID logo ,
Seshadri S. Vasan
* ORCID logo
Version 1 : Received: 19 September 2022 / Approved: 20 September 2022 / Online: 20 September 2022 (15:00:48 CEST)

A peer-reviewed article of this Preprint also exists.

MacRaild, C.A.; Mohammed, M.-U.-R.; Faheem; Murugesan, S.; Styles, I.K.; Peterson, A.L.; Kirkpatrick, C.M.J.; Cooper, M.A.; Palombo, E.A.; Simpson, M.M.; Jain, H.A.; Agarwal, V.; McAuley, A.J.; Kumar, A.; Creek, D.J.; Trevaskis, N.L.; Vasan, S.S. Systematic Down-Selection of Repurposed Drug Candidates for COVID-19. Int. J. Mol. Sci. 2022, 23, 11851. MacRaild, C.A.; Mohammed, M.-U.-R.; Faheem; Murugesan, S.; Styles, I.K.; Peterson, A.L.; Kirkpatrick, C.M.J.; Cooper, M.A.; Palombo, E.A.; Simpson, M.M.; Jain, H.A.; Agarwal, V.; McAuley, A.J.; Kumar, A.; Creek, D.J.; Trevaskis, N.L.; Vasan, S.S. Systematic Down-Selection of Repurposed Drug Candidates for COVID-19. Int. J. Mol. Sci. 2022, 23, 11851.

Abstract

SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA approved molecules with established safety profiles that have a plausible mechanism for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising repurposable drug candidates that are safe, efficacious, and cost-effective for the treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx, https://www.covirx.org/) that was also developed to enable scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.

Keywords

COVID-19; CoviRx.org; database; drugs; pandemic; repurposing; SARS-CoV-2; therapies; treatments; Variants of Concern (VOC)

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.