Oral drug repositioning candidates and synergistic remdesivir combinations for the prophylaxis and treatment of COVID-19
Malina A. Bakowski,
Tu-Trinh H. Nguyen,
Melanie G. Kirkpatrick,
Anil K. Gupta,
Mitchell V. Hull,
Peter G. Schultz,
Dennis R. Burton,
Arnab K. Chatterjee,
Case W McNamara,
Thomas F Rogers
Posted 16 Jun 2020
bioRxiv DOI: 10.1101/2020.06.16.153403
Posted 16 Jun 2020
The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. A high-throughput, high-content imaging assay of human HeLa cells expressing the SARS-CoV-2 receptor ACE2 was used to screen ReFRAME, a best-in-class drug repurposing library. From nearly 12,000 compounds, we identified 66 compounds capable of selectively inhibiting SARS-CoV-2 replication in human cells. Twenty-four of these drugs show additive activity in combination with the RNA-dependent RNA polymerase inhibitor remdesivir and may afford increased in vivo efficacy. We also identified synergistic interaction of the nucleoside analog riboprine and a folate antagonist 10-deazaaminopterin with remdesivir. Overall, seven clinically approved drugs (halofantrine, amiodarone, nelfinavir, simeprevir, manidipine, ozanimod, osimertinib) and 19 compounds in other stages of development may have the potential to be repurposed as SARS-CoV-2 oral therapeutics based on their potency, pharmacokinetic and human safety profiles. ### Competing Interest Statement The authors have declared no competing interest.
- Downloaded 959 times
- Download rankings, all-time:
- Site-wide: 18,260 out of 118,977
- In microbiology: 1,010 out of 9,394
- Year to date:
- Site-wide: 6,384 out of 118,977
- Since beginning of last month:
- Site-wide: 7,347 out of 118,977
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!