Lessons Learned From Limited Overlap of 15 In Vitro COVID-19 Drug Repurposing Screens

Overview

Journal Health Secur

Specialty Emergency Medicine

Date 2023 May 17

PMID 37196212

Authors

Phillip J Tomezsko

Cassandra W Phillipson

Matthew E Walsh

Affiliations

Soon will be listed here.

Abstract

Drug repurposing can quickly and cost-effectively identify medical countermeasures against pathogens with pandemic potential and could be used as a down-selection method for selecting US Food and Drug Administration-approved drugs to test in clinical trials. We compared results from 15 high-throughput in vitro screening efforts that tested approved and clinically evaluated drugs for activity against SARS-CoV-2 replication. From the 15 studies, 304 drugs were identified as displaying the highest level of confidence from the individual screens. Of those 304 drugs, 30 were identified in 2 or more screens, while only 3 drugs (apilimod, tetrandrine, and salinomycin) were identified in 4 screens. The lack of concordance in high-confidence hits and variations in protocols makes it challenging to use the collective data as down-selection criteria for identifying repurposing candidates to move into a clinical trial.

References

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

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

Pushpakom S, Iorio F, Eyers P, Jane Escott K, Hopper S, Wells A . Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2018; 18(1):41-58. DOI: 10.1038/nrd.2018.168. View

Holwerda M, Vkovski P, Wider M, Thiel V, Dijkman R . Identification of an Antiviral Compound from the Pandemic Response Box that Efficiently Inhibits SARS-CoV-2 Infection In Vitro. Microorganisms. 2020; 8(12). PMC: 7760777. DOI: 10.3390/microorganisms8121872. View

Ellinger B, Bojkova D, Zaliani A, Cinatl J, Claussen C, Westhaus S . A SARS-CoV-2 cytopathicity dataset generated by high-content screening of a large drug repurposing collection. Sci Data. 2021; 8(1):70. PMC: 7910569. DOI: 10.1038/s41597-021-00848-4. View

Bakowski M, Beutler N, Wolff K, Kirkpatrick M, Chen E, Nguyen T . Drug repurposing screens identify chemical entities for the development of COVID-19 interventions. Nat Commun. 2021; 12(1):3309. PMC: 8175350. DOI: 10.1038/s41467-021-23328-0. View

Mirabelli C, Wotring J, Zhang C, McCarty S, Fursmidt R, Pretto C . Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19. Proc Natl Acad Sci U S A. 2021; 118(36). PMC: 8433531. DOI: 10.1073/pnas.2105815118. View

Biering S, Van Dis E, Wehri E, Yamashiro L, Nguyenla X, Dugast-Darzacq C . Screening a Library of FDA-Approved and Bioactive Compounds for Antiviral Activity against SARS-CoV-2. ACS Infect Dis. 2021; 7(8):2337-2351. DOI: 10.1021/acsinfecdis.1c00017. View

Touret F, Gilles M, Barral K, Nougairede A, van Helden J, Decroly E . In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication. Sci Rep. 2020; 10(1):13093. PMC: 7403393. DOI: 10.1038/s41598-020-70143-6. View

10.

Edwards A . What Are the Odds of Finding a COVID-19 Drug from a Lab Repurposing Screen?. J Chem Inf Model. 2020; 60(12):5727-5729. DOI: 10.1021/acs.jcim.0c00861. View

11.

Riva L, Yuan S, Yin X, Martin-Sancho L, Matsunaga N, Pache L . Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature. 2020; 586(7827):113-119. PMC: 7603405. DOI: 10.1038/s41586-020-2577-1. View

12.

Wouters O, Mckee M, Luyten J . Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020; 323(9):844-853. PMC: 7054832. DOI: 10.1001/jama.2020.1166. View

13.

Ku K, Shin H, Kim H, Kim B, Kim S, Kim C . Repurposing Screens of FDA-Approved Drugs Identify 29 Inhibitors of SARS-CoV-2. J Microbiol Biotechnol. 2020; 30(12):1843-1853. PMC: 9728307. DOI: 10.4014/jmb.2009.09009. View

14.

Chen C, Shinn P, Itkin Z, Eastman R, Bostwick R, Rasmussen L . Drug Repurposing Screen for Compounds Inhibiting the Cytopathic Effect of SARS-CoV-2. Front Pharmacol. 2021; 11:592737. PMC: 7942396. DOI: 10.3389/fphar.2020.592737. View

15.

Jan J, Cheng T, Juang Y, Ma H, Wu Y, Yang W . Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection. Proc Natl Acad Sci U S A. 2021; 118(5). PMC: 7865145. DOI: 10.1073/pnas.2021579118. View

16.

Yuan S, Chan J, Chik K, Chan C, Tsang J, Liang R . Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system. Pharmacol Res. 2020; 159:104960. PMC: 7254006. DOI: 10.1016/j.phrs.2020.104960. View