Drug Repurposing Screen for Compounds Inhibiting the Cytopathic Effect of SARS-CoV-2

Overview

Journal Front Pharmacol

Date 2021 Mar 12

PMID 33708112

Citations 58

Authors

Catherine Z Chen

Paul Shinn

Zina Itkin

Richard T Eastman

Robert Bostwick

Lynn Rasmussen

Ruili Huang

Min Shen

Xin Hu

Kelli M Wilson

Brianna M Brooks

Hui Guo

Tongan Zhao

Carleen Klump-Thomas

Anton Simeonov

Samuel G Michael

Donald C Lo

Matthew D Hall

Wei Zheng

Affiliations

Soon will be listed here.

Abstract

Drug repurposing is a rapid approach to identify therapeutics for the treatment of emerging infectious diseases such as COVID-19. To address the urgent need for treatment options, we carried out a quantitative high-throughput screen using a SARS-CoV-2 cytopathic assay with a compound collection of 8,810 approved and investigational drugs, mechanism-based bioactive compounds, and natural products. Three hundred and nineteen compounds with anti-SARS-CoV-2 activities were identified and confirmed, including 91 approved drugs and 49 investigational drugs. The anti-SARS-CoV-2 activities of 230 of these confirmed compounds, of which 38 are approved drugs, have not been previously reported. Chlorprothixene, methotrimeprazine, and piperacetazine were the three most potent FDA-approved drugs with anti-SARS-CoV-2 activities. These three compounds have not been previously reported to have anti-SARS-CoV-2 activities, although their antiviral activities against SARS-CoV and Ebola virus have been reported. These results demonstrate that this comprehensive data set is a useful resource for drug repurposing efforts, including design of new drug combinations for clinical trials for SARS-CoV-2.

Citing Articles

Hexestrol, an estrogen receptor agonist, inhibits Lassa virus entry.

Zhang Z, Takenaga T, Fehling S, Igarashi M, Hirokawa T, Muramoto Y J Virol. 2024; 98(7):e0071424.

PMID: 38809021 PMC: 11265444. DOI: 10.1128/jvi.00714-24.

COVID-19 drug discovery and treatment options.

Chan J, Yuan S, Chu H, Sridhar S, Yuen K Nat Rev Microbiol. 2024; 22(7):391-407.

PMID: 38622352 DOI: 10.1038/s41579-024-01036-y.

Binding Activity Classification of Anti-SARS-CoV-2 Molecules using Deep Learning Across Multiple Assays.

Yamasan B, Korkmaz S Balkan Med J. 2024; 41(3):186-192.

PMID: 38462979 PMC: 11077922. DOI: 10.4274/balkanmedj.galenos.2024.2024-1-73.

Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity.

Sami Alkafaas S, Abdallah A, Hassan M, Hussien A, Samy ElKafas S, Loutfy S BMC Public Health. 2024; 24(1):395.

PMID: 38321448 PMC: 10848368. DOI: 10.1186/s12889-024-17747-z.

The Virus-Induced Cytopathic Effect.

Cespedes-Tenorio D, Arias-Arias J Subcell Biochem. 2023; 106:197-210.

PMID: 38159228 DOI: 10.1007/978-3-031-40086-5_7.

References

Dittmar M, Lee J, Whig K, Segrist E, Li M, Kamalia B . Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2. Cell Rep. 2021; 35(1):108959. PMC: 7985926. DOI: 10.1016/j.celrep.2021.108959. View

Eastman R, Roth J, Brimacombe K, Simeonov A, Shen M, Patnaik S . Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent Sci. 2020; 6(5):672-683. PMC: 7202249. DOI: 10.1021/acscentsci.0c00489. View

Huang R, Zhu H, Shinn P, Ngan D, Ye L, Thakur A . The NCATS Pharmaceutical Collection: a 10-year update. Drug Discov Today. 2019; 24(12):2341-2349. DOI: 10.1016/j.drudis.2019.09.019. View

Jiang Y, Liu L, Manning M, Bonahoom M, Lotvola A, Yang Z . Structural analysis, virtual screening and molecular simulation to identify potential inhibitors targeting 2'-O-ribose methyltransferase of SARS-CoV-2 coronavirus. J Biomol Struct Dyn. 2020; 40(3):1331-1346. PMC: 7544923. DOI: 10.1080/07391102.2020.1828172. View

Inglese J, Auld D, Jadhav A, Johnson R, Simeonov A, Yasgar A . Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries. Proc Natl Acad Sci U S A. 2006; 103(31):11473-8. PMC: 1518803. DOI: 10.1073/pnas.0604348103. View

Zhang H, Zhong D, Zhang Z, Dai X, Chen X . Liquid chromatography/tandem mass spectrometry method for the quantification of deserpidine in human plasma: Application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877(27):3221-5. DOI: 10.1016/j.jchromb.2009.06.005. View

Huang R, Xu M, Zhu H, Chen C, Zhu W, Lee E . Biological activity-based modeling identifies antiviral leads against SARS-CoV-2. Nat Biotechnol. 2021; 39(6):747-753. PMC: 9843700. DOI: 10.1038/s41587-021-00839-1. View

Shrimp J, Kales S, Sanderson P, Simeonov A, Shen M, Hall M . An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19. ACS Pharmacol Transl Sci. 2020; 3(5):997-1007. PMC: 7507803. DOI: 10.1021/acsptsci.0c00106. View

Ryu Y, Park S, Kim Y, Lee J, Seo W, Chang J . SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii. Bioorg Med Chem Lett. 2010; 20(6):1873-6. PMC: 7127101. DOI: 10.1016/j.bmcl.2010.01.152. View

10.

Zhu W, Xu M, Chen C, Guo H, Shen M, Hu X . Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening. ACS Pharmacol Transl Sci. 2020; 3(5):1008-1016. PMC: 7507806. DOI: 10.1021/acsptsci.0c00108. View

11.

Heaton N . Revisiting the concept of a cytopathic viral infection. PLoS Pathog. 2017; 13(7):e1006409. PMC: 5519205. DOI: 10.1371/journal.ppat.1006409. View

12.

Ou X, Liu Y, Lei X, Li P, Mi D, Ren L . Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020; 11(1):1620. PMC: 7100515. DOI: 10.1038/s41467-020-15562-9. View

13.

Beigel J, Tomashek K, Dodd L, Mehta A, Zingman B, Kalil A . Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020; 383(19):1813-1826. PMC: 7262788. DOI: 10.1056/NEJMoa2007764. View

14.

Winstanley P, Edwards G, Orme M, Breckenridge A . The disposition of amodiaquine in man after oral administration. Br J Clin Pharmacol. 1987; 23(1):1-7. PMC: 1386133. DOI: 10.1111/j.1365-2125.1987.tb03002.x. View

15.

Dwivedy A, Mariadasse R, Ahmad M, Chakraborty S, Kar D, Tiwari S . Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2. PLoS Comput Biol. 2021; 17(9):e1009384. PMC: 8478224. DOI: 10.1371/journal.pcbi.1009384. View

16.

Zimniak M, Kirschner L, Hilpert H, Geiger N, Danov O, Oberwinkler H . The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue. Sci Rep. 2021; 11(1):5890. PMC: 7961020. DOI: 10.1038/s41598-021-85049-0. View

17.

Weston S, Coleman C, Haupt R, Logue J, Matthews K, Li Y . Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 and SARS-CoV . J Virol. 2020; 94(21). PMC: 7565640. DOI: 10.1128/JVI.01218-20. View

18.

Ianevski A, Yao R, Fenstad M, Biza S, Zusinaite E, Reisberg T . Potential Antiviral Options against SARS-CoV-2 Infection. Viruses. 2020; 12(6). PMC: 7354438. DOI: 10.3390/v12060642. View

19.

Jeon S, Ko M, Lee J, Choi I, Byun S, Park S . Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs. Antimicrob Agents Chemother. 2020; 64(7). PMC: 7318052. DOI: 10.1128/AAC.00819-20. View

20.

Morales-Ortega A, Bernal-Bello D, Llarena-Barroso C, Frutos-Perez B, Duarte-Millan M, Garcia de Viedma-Garcia V . Imatinib for COVID-19: A case report. Clin Immunol. 2020; 218:108518. PMC: 7319919. DOI: 10.1016/j.clim.2020.108518. View