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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Review Article

A Brief Study on Drug Repurposing: New Way of Boosting Drug Discovery

Author(s): Kamal Kant Kaushik, Rupa Mazumder*, Abhijit Debnath and Manisha Patel

Volume 20, Issue 3, 2023

Published on: 06 October, 2022

Page: [264 - 278] Pages: 15

DOI: 10.2174/1570180819666220901170016

Price: $65

Abstract

Background: Even with the massive increase in financial investments in pharmaceutical research over the last decade, the number of new drugs approved has plummeted. As a result, finding new uses for approved pharmaceuticals has become a prominent alternative approach for the pharmaceutical industry.

Objective: Drug repurposing or repositioning is a game-changing development in the field of drug research that entails discovering additional uses for previously approved drugs.

Methods: In comparison to traditional drug discovery methods, drug repositioning enhances the preclinical steps of creating innovative medications by reducing the cost and time of the process. Drug repositioning depends heavily on available drug-disease data, so the fast development of available data as well as developed computing skills has resulted in the boosting of various new drug repositioning methods. The main goal of this article is to describe these different methods and approaches for drug repurposing.

Results: The article describes the basic concept of drug repurposing, its significance in discovering new medications for various disorders, drug repurposing approaches such as computational and experimental approaches, and previous as well as recent applications of drug repurposing in diseases such as cancer, COVID-19, and orphan diseases.

Conclusion: The review also addresses obstacles in drug development using drug repurposing strategies, such as a lack of financing and regulatory concerns and concludes with outlining recommendations for overcoming these challenges.

Keywords: Drug repurposing, Drug repositioning, Computational methods, Machine learning, Docking, Pharmacogenomics, Orphan diseases, COVID-19, Cancer.

Graphical Abstract

[1]
Eisenstein, E.L.; Lemons, P.W., II; Tardiff, B.E.; Schulman, K.A.; Jolly, M.K.; Califf, R.M. Reducing the costs of phase III cardiovascular clinical trials. Am. Heart J., 2005, 149(3), 482-488.
[http://dx.doi.org/10.1016/j.ahj.2004.04.049] [PMID: 15864237]
[2]
Sertkaya, A.; Birkenbach, A.; Berlind, A.; Eyraud, J. Examination of clinical trial costs and barriers for drug development. US Department of Health and Human Services, ASPE. 2014, 1-92.
[3]
Yeu, Y.; Yoon, Y.; Park, S. Protein localization vector propagation: A method for improving the accuracy of drug repositioning. Mol. Biosyst., 2015, 11(7), 2096-2102.
[http://dx.doi.org/10.1039/C5MB00306G] [PMID: 25998487]
[4]
Law, G.L.; Tisoncik-Go, J.; Korth, M.J.; Katze, M.G. Drug repurposing: A better approach for infectious disease drug discovery? Curr. Opin. Immunol., 2013, 25(5), 588-592.
[http://dx.doi.org/10.1016/j.coi.2013.08.004] [PMID: 24011665]
[5]
Xue, H.; Li, J.; Xie, H.; Wang, Y. Review of drug repositioning approaches and resources. Int. J. Biol. Sci., 2018, 14(10), 1232-1244.
[http://dx.doi.org/10.7150/ijbs.24612] [PMID: 30123072]
[6]
Ashburn, T.T.; Thor, K.B. Drug repositioning: Identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[7]
Graul, A.I.; Sorbera, L.; Pina, P.; Tell, M.; Cruces, E.; Rosa, E.; Stringer, M.; Castañer, R.; Revel, L. The year’s new drugs & biologics - 2009. Drug News Perspect., 2010, 23(1), 7-36.
[http://dx.doi.org/10.1358/dnp.2010.23.1.1440373] [PMID: 20155217]
[8]
Parisi, D.; Adasme, M.F.; Sveshnikova, A.; Bolz, S.N.; Moreau, Y.; Schroeder, M. Drug repositioning or target repositioning: A structural perspective of drug-target-indication relationship for available repurposed drugs. Comput. Struct. Biotechnol. J., 2020, 18, 1043-1055.
[http://dx.doi.org/10.1016/j.csbj.2020.04.004] [PMID: 32419905]
[9]
Pushpakom, S.; Iorio, F.; Eyers, P.A.; Escott, K.J.; Hopper, S.; Wells, A.; Doig, A.; Guilliams, T.; Latimer, J.; McNamee, C.; Norris, A.; Sanseau, P.; Cavalla, D.; Pirmohamed, M. Drug repurposing: Progress, challenges and recommendations. Nat. Rev. Drug Discov., 2019, 18(1), 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[10]
Hodos, R.A.; Kidd, B.A.; Khader, S.; Readhead, B.P.; Dudley, J.T. In silico methods for drug repurposing and pharmacology. Wiley Interdiscip. Rev. Syst. Biol. Med., 2016, 8(3), 186-210.
[http://dx.doi.org/10.1002/wsbm.1337] [PMID: 27080087]
[11]
Keiser, M.J.; Setola, V.; Irwin, J.J.; Laggner, C.; Abbas, A.I.; Hufeisen, S.J.; Jensen, N.H.; Kuijer, M.B.; Matos, R.C.; Tran, T.B.; Whaley, R.; Glennon, R.A.; Hert, J.; Thomas, K.L.H.; Edwards, D.D.; Shoichet, B.K.; Roth, B.L. Predicting new molecular targets for known drugs. Nature, 2009, 462(7270), 175-181.
[http://dx.doi.org/10.1038/nature08506] [PMID: 19881490]
[12]
Le, B.L.; Iwatani, S.; Wong, R.J.; Stevenson, D.K.; Sirota, M. Computational discovery of therapeutic candidates for preventing preterm birth. JCI Insight, 2020, 5(3), e133761.
[http://dx.doi.org/10.1172/jci.insight.133761] [PMID: 32051340]
[13]
Brown, A.S.; Patel, C.J. MeSHDD: Literature-based drug-drug similarity for drug repositioning. J. Am. Med. Inform. Assoc., 2017, 24(3), 614-618.
[http://dx.doi.org/10.1093/jamia/ocw142] [PMID: 27678460]
[14]
Low, Z.Y.; Farouk, I.A.; Lal, S.K. Drug repositioning: New approaches and future prospects for life-debilitating diseases and the COVID-19 pandemic outbreak. Viruses, 2020, 12(9), 1058.
[http://dx.doi.org/10.3390/v12091058] [PMID: 32972027]
[15]
Oprea, T.I.; Tropsha, A.; Faulon, J.L.; Rintoul, M.D. Systems chemical biology. Nat. Chem. Biol., 2007, 3(8), 447-450.
[http://dx.doi.org/10.1038/nchembio0807-447] [PMID: 17637771]
[16]
Dudley, J.T.; Deshpande, T.; Butte, A.J. Exploiting drug-disease relationships for computational drug repositioning. Brief. Bioinform., 2011, 12(4), 303-311.
[http://dx.doi.org/10.1093/bib/bbr013] [PMID: 21690101]
[17]
Yang, L.; Agarwal, P. Systematic drug repositioning based on clinical side-effects. PLoS One, 2011, 6(12), e28025.
[http://dx.doi.org/10.1371/journal.pone.0028025] [PMID: 22205936]
[18]
Agarwal, S.; Mehrotra, R. An overview of molecular docking. JSM Chem., 2016, 4(2), 1024-1028.
[19]
Wang, F.; Wu, F.X.; Li, C.Z.; Jia, C.Y.; Su, S.W.; Hao, G.F.; Yang, G.F. ACID: A free tool for drug repurposing using consensus inverse docking strategy. J. Cheminform., 2019, 11(1), 73.
[http://dx.doi.org/10.1186/s13321-019-0394-z] [PMID: 33430982]
[20]
Chaudhari, R.; Tan, Z.; Huang, B.; Zhang, S. Computational polypharmacology: A new paradigm for drug discovery. Expert Opin. Drug Discov., 2017, 12(3), 279-291.
[http://dx.doi.org/10.1080/17460441.2017.1280024] [PMID: 28067061]
[21]
Li, H.; Gao, Z.; Kang, L.; Zhang, H.; Yang, K.; Yu, K.; Luo, X.; Zhu, W.; Chen, K.; Shen, J.; Wang, X.; Jiang, H. TarFisDock: A web server for identifying drug targets with docking approach. Nucleic Acids Res., 2006, 34(Suppl. 2), W219-W224.
[http://dx.doi.org/10.1093/nar/gkl114] [PMID: 16844997]
[22]
Gao, Z.; Li, H.; Zhang, H.; Liu, X.; Kang, L.; Luo, X.; Zhu, W.; Chen, K.; Wang, X.; Jiang, H. PDTD: A web-accessible protein database for drug target identification. BMC Bioinformatics, 2008, 9(1), 104.
[http://dx.doi.org/10.1186/1471-2105-9-104] [PMID: 18282303]
[23]
Wang, J.C.; Chu, P.Y.; Chen, C.M.; Lin, J.H. idTarget: A web server for identifying protein targets of small chemical molecules with robust scoring functions and a divide-and-conquer docking approach. Nucleic Acids Res., 2012, 40(W1), W393-W399.
[http://dx.doi.org/10.1093/nar/gks496] [PMID: 22649057]
[24]
Dakshanamurthy, S.; Issa, N.T.; Assefnia, S.; Seshasayee, A.; Peters, O.J.; Madhavan, S.; Uren, A.; Brown, M.L.; Byers, S.W. Predicting new indications for approved drugs using a proteochemometric method. J. Med. Chem., 2012, 55(15), 6832-6848.
[http://dx.doi.org/10.1021/jm300576q] [PMID: 22780961]
[25]
Park, K. A review of computational drug repurposing. Transl. Clin. Pharmacol., 2019, 27(2), 59-63.
[http://dx.doi.org/10.12793/tcp.2019.27.2.59] [PMID: 32055582]
[26]
Azuaje, F. Drug interaction networks: An introduction to translational and clinical applications. Cardiovasc. Res., 2013, 97(4), 631-641.
[http://dx.doi.org/10.1093/cvr/cvs289] [PMID: 22977007]
[27]
Iorio, F.; Bosotti, R.; Scacheri, E.; Belcastro, V.; Mithbaokar, P.; Ferriero, R.; Murino, L.; Tagliaferri, R.; Brunetti-Pierri, N.; Isacchi, A.; di Bernardo, D. Discovery of drug mode of action and drug repositioning from transcriptional responses. Proc. Natl. Acad. Sci. USA, 2010, 107(33), 14621-14626.
[http://dx.doi.org/10.1073/pnas.1000138107] [PMID: 20679242]
[28]
Iorio, F.; Rittman, T.; Ge, H.; Menden, M.; Saez-Rodriguez, J. Transcriptional data: A new gateway to drug repositioning? Drug Discov. Today, 2013, 18(7-8), 350-357.
[http://dx.doi.org/10.1016/j.drudis.2012.07.014] [PMID: 22897878]
[29]
Dhir, N.; Jain, A.; Mahendru, D.; Prakash, A.; Medhi, B. Drug Repurposing and Orphan Disease Therapeutics. In: Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications; Badria, F.A., Ed.; IntechOpen: London, 2020; pp. 63-77.
[http://dx.doi.org/10.5772/intechopen.91941]
[30]
Sanseau, P.; Agarwal, P.; Barnes, M.R.; Pastinen, T.; Richards, J.B.; Cardon, L.R.; Mooser, V. Use of genome-wide association studies for drug repositioning. Nat. Biotechnol., 2012, 30(4), 317-320.
[http://dx.doi.org/10.1038/nbt.2151] [PMID: 22491277]
[31]
Huang, Y.H.; Vakoc, C.R. A biomarker harvest from one thousand cancer cell lines. Cell, 2016, 166(3), 536-537.
[http://dx.doi.org/10.1016/j.cell.2016.07.010] [PMID: 27471963]
[32]
Weinstein, J.N. Cell lines battle cancer. Nature, 2012, 483(7391), 544-545.
[http://dx.doi.org/10.1038/483544a] [PMID: 22460893]
[33]
Barretina, J.; Caponigro, G.; Stransky, N.; Venkatesan, K.; Margolin, A.A.; Kim, S.; Wilson, C.J.; Lehár, J.; Kryukov, G.V.; Sonkin, D.; Reddy, A.; Liu, M.; Murray, L.; Berger, M.F.; Monahan, J.E.; Morais, P.; Meltzer, J.; Korejwa, A.; Jané-Valbuena, J.; Mapa, F.A.; Thibault, J.; Bric-Furlong, E.; Raman, P.; Shipway, A.; Engels, I.H.; Cheng, J.; Yu, G.K.; Yu, J.; Aspesi, P., Jr; de Silva, M.; Jagtap, K.; Jones, M.D.; Wang, L.; Hatton, C.; Palescandolo, E.; Gupta, S.; Mahan, S.; Sougnez, C.; Onofrio, R.C.; Liefeld, T.; MacConaill, L.; Winckler, W.; Reich, M.; Li, N.; Mesirov, J.P.; Gabriel, S.B.; Getz, G.; Ardlie, K.; Chan, V.; Myer, V.E.; Weber, B.L.; Porter, J.; Warmuth, M.; Finan, P.; Harris, J.L.; Meyerson, M.; Golub, T.R.; Morrissey, M.P.; Sellers, W.R.; Schlegel, R.; Garraway, L.A. The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature, 2012, 483(7391), 603-607.
[http://dx.doi.org/10.1038/nature11003] [PMID: 22460905]
[34]
Basu, A.; Bodycombe, N.E.; Cheah, J.H.; Price, E.V.; Liu, K.; Schaefer, G.I.; Ebright, R.Y.; Stewart, M.L.; Ito, D.; Wang, S.; Bracha, A.L.; Liefeld, T.; Wawer, M.; Gilbert, J.C.; Wilson, A.J.; Stransky, N.; Kryukov, G.V.; Dancik, V.; Barretina, J.; Garraway, L.A.; Hon, C.S.Y.; Munoz, B.; Bittker, J.A.; Stockwell, B.R.; Khabele, D.; Stern, A.M.; Clemons, P.A.; Shamji, A.F.; Schreiber, S.L. An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules. Cell, 2013, 154(5), 1151-1161.
[http://dx.doi.org/10.1016/j.cell.2013.08.003] [PMID: 23993102]
[35]
Seashore-Ludlow, B.; Rees, M.G.; Cheah, J.H.; Cokol, M.; Price, E.V.; Coletti, M.E.; Jones, V.; Bodycombe, N.E.; Soule, C.K.; Gould, J.; Alexander, B.; Li, A.; Montgomery, P.; Wawer, M.J.; Kuru, N.; Kotz, J.D.; Hon, C.S.Y.; Munoz, B.; Liefeld, T. Dančík, V.; Bittker, J.A.; Palmer, M.; Bradner, J.E.; Shamji, A.F.; Clemons, P.A.; Schreiber, S.L. Harnessing connectivity in a large-scale small-molecule sensitivity dataset. Cancer Discov., 2015, 5(11), 1210-1223.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0235] [PMID: 26482930]
[36]
Iorio, F.; Knijnenburg, T.A.; Vis, D.J.; Bignell, G.R.; Menden, M.P.; Schubert, M.; Aben, N.; Gonçalves, E.; Barthorpe, S.; Lightfoot, H.; Cokelaer, T.; Greninger, P.; van Dyk, E.; Chang, H.; de Silva, H.; Heyn, H.; Deng, X.; Egan, R.K.; Liu, Q.; Mironenko, T.; Mitropoulos, X.; Richardson, L.; Wang, J.; Zhang, T.; Moran, S.; Sayols, S.; Soleimani, M.; Tamborero, D.; Lopez-Bigas, N.; Ross-Macdonald, P.; Esteller, M.; Gray, N.S.; Haber, D.A.; Stratton, M.R.; Benes, C.H.; Wessels, L.F.A.; Saez-Rodriguez, J.; McDermott, U.; Garnett, M.J. A landscape of pharmacogenomic interactions in cancer. Cell, 2016, 166(3), 740-754.
[http://dx.doi.org/10.1016/j.cell.2016.06.017] [PMID: 27397505]
[37]
Wei, W.Q.; Denny, J.C. Extracting research-quality phenotypes from electronic health records to support precision medicine. Genome Med., 2015, 7(1), 41.
[http://dx.doi.org/10.1186/s13073-015-0166-y] [PMID: 25937834]
[38]
Xu, H.; Aldrich, M.C.; Chen, Q.; Liu, H.; Peterson, N.B.; Dai, Q.; Levy, M.; Shah, A.; Han, X.; Ruan, X.; Jiang, M.; Li, Y.; Julien, J.S.; Warner, J.; Friedman, C.; Roden, D.M.; Denny, J.C. Validating drug repurposing signals using electronic health records: A case study of metformin associated with reduced cancer mortality. J. Am. Med. Inform. Assoc., 2015, 22(1), 179-191.
[http://dx.doi.org/10.1136/amiajnl-2014-002649] [PMID: 25053577]
[39]
Jarada, T.N.; Rokne, J.G.; Alhajj, R. A review of computational drug repositioning: Strategies, approaches, opportunities, challenges, and directions. J. Cheminform., 2020, 12(1), 46.
[http://dx.doi.org/10.1186/s13321-020-00450-7] [PMID: 33431024]
[40]
Zhao, K.; So, H. C A machine learning approach to drug repositioning based on drug expression profiles: Applications to schizophrenia and depression/anxiety disorders. Arxiv: Genomics, 2017.
[41]
Cavalla, D.; Singal, C. Retrospective clinical analysis for drug rescue: For new indications or stratified patient groups. Drug Discov. Today, 2012, 17(3-4), 104-109.
[http://dx.doi.org/10.1016/j.drudis.2011.09.019] [PMID: 22001144]
[42]
Rothwell, P.M.; Fowkes, F.G.R.; Belch, J.F.F.; Ogawa, H.; Warlow, C.P.; Meade, T.W. Effect of daily aspirin on long-term risk of death due to cancer: Analysis of individual patient data from randomised trials. Lancet, 2011, 377(9759), 31-41.
[http://dx.doi.org/10.1016/S0140-6736(10)62110-1] [PMID: 21144578]
[43]
Zou, H.; Zhang, Q.; Guo, Z.; Guo, B.; Zhang, Q.; Chen, X. A mass spectrometry based direct binding assay for screening binding partners of proteins. Angew. Chem., 2002, 114(4), 668-670.
[http://dx.doi.org/10.1002/1521-3757(20020215)114:4<668:AID-ANGE668>3.0.CO;2-N]
[44]
Brehmer, D.; Greff, Z.; Godl, K.; Blencke, S.; Kurtenbach, A.; Weber, M.; Müller, S.; Klebl, B.; Cotten, M.; Kéri, G.; Wissing, J.; Daub, H. Cellular targets of gefitinib. Cancer Res., 2005, 65(2), 379-382.
[http://dx.doi.org/10.1158/0008-5472.379.65.2] [PMID: 15695376]
[45]
Martinez Molina, D.; Nordlund, P. The cellular thermal shift assay: A novel biophysical assay for in situ drug target engagement and mechanistic biomarker studies. Annu. Rev. Pharmacol. Toxicol., 2016, 56(1), 141-161.
[http://dx.doi.org/10.1146/annurev-pharmtox-010715-103715] [PMID: 26566155]
[46]
Moffat, J.G.; Vincent, F.; Lee, J.A.; Eder, J.; Prunotto, M. Opportunities and challenges in phenotypic drug discovery: An industry perspective. Nat. Rev. Drug Discov., 2017, 16(8), 531-543.
[http://dx.doi.org/10.1038/nrd.2017.111] [PMID: 28685762]
[47]
Cousin, M.A.; Ebbert, J.O.; Wiinamaki, A.R.; Urban, M.D.; Argue, D.P.; Ekker, S.C.; Klee, E.W. Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment. PLoS One, 2014, 9(3), e90467.
[http://dx.doi.org/10.1371/journal.pone.0090467] [PMID: 24658307]
[48]
Naylor, S.; Schonfeld, J.M. Therapeutic drug repurposing, repositioning and rescue - part I: Overview. Drug Discovery World., 2014, 16(1), 49-62.
[49]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin., 2022, 72(1), 7-33.
[http://dx.doi.org/10.3322/caac.21708] [PMID: 35020204]
[50]
Shaked, Y. The pro-tumorigenic host response to cancer therapies. Nat. Rev. Cancer, 2019, 19(12), 667-685.
[http://dx.doi.org/10.1038/s41568-019-0209-6] [PMID: 31645711]
[51]
Kirsch, J.; Siltanen, C.; Zhou, Q.; Revzin, A.; Simonian, A. Biosensor technology: Recent advances in threat agent detection and medicine. Chem. Soc. Rev., 2013, 42(22), 8733-8768.
[http://dx.doi.org/10.1039/c3cs60141b] [PMID: 23852443]
[52]
Lin, C.C.; Suen, K.M.; Stainthorp, A.; Wieteska, L.; Biggs, G.S.; Leitão, A.; Montanari, C.A.; Ladbury, J.E. Targeting the Shc-EGFR interaction with indomethacin inhibits MAP kinase pathway signalling. Cancer Lett., 2019, 457, 86-97.
[http://dx.doi.org/10.1016/j.canlet.2019.05.008] [PMID: 31100409]
[53]
Pollak, M. Overcoming drug development bottlenecks with repurposing: Repurposing biguanides to target energy metabolism for cancer treatment. Nat. Med., 2014, 20(6), 591-593.
[http://dx.doi.org/10.1038/nm.3596] [PMID: 24901568]
[54]
Liang, G.; Liu, M.; Wang, Q.; Shen, Y.; Mei, H.; Li, D.; Liu, W. Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K/mTOR signaling pathways. Oncotarget, 2017, 8(17), 28510-28525.
[http://dx.doi.org/10.18632/oncotarget.15324] [PMID: 28212537]
[55]
Kumar, S.; Bryant, C.S.; Chamala, S.; Qazi, A.; Seward, S.; Pal, J.; Steffes, C.P.; Weaver, D.W.; Morris, R.; Malone, J.M.; Shammas, M.A.; Prasad, M.; Batchu, R.B. Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells. Mol. Cancer, 2009, 8(1), 26.
[http://dx.doi.org/10.1186/1476-4598-8-26] [PMID: 19386116]
[56]
Srirangam, A.; Milani, M.; Mitra, R.; Guo, Z.; Rodriguez, M.; Kathuria, H.; Fukuda, S.; Rizzardi, A.; Schmechel, S.; Skalnik, D.G.; Pelus, L.M.; Potter, D.A. The human immunodeficiency virus protease inhibitor ritonavir inhibits lung cancer cells, in part, by inhibition of survivin. J. Thorac. Oncol., 2011, 6(4), 661-670.
[http://dx.doi.org/10.1097/JTO.0b013e31820c9e3c] [PMID: 21270666]
[57]
Batchu, R.; Gruzdyn, O.; Bryant, C.; Qazi, A.; Kumar, S.; Chamala, S.; Kung, S.; Sanka, R.; Puttagunta, U.; Weaver, D.; Gruber, S. Ritonavir-mediated induction of apoptosis in pancreatic cancer occurs via the RB/E2F-1 and AKT pathways. Pharmaceuticals, 2014, 7(1), 46-57.
[http://dx.doi.org/10.3390/ph7010046] [PMID: 24451403]
[58]
Chen, B.; Wei, W.; Ma, L.; Yang, B.; Gill, R.M.; Chua, M.S.; Butte, A.J.; So, S. Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells in vitro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology, 2017, 152(8), 2022-2036.
[http://dx.doi.org/10.1053/j.gastro.2017.02.039] [PMID: 28284560]
[59]
Sack, U.; Walther, W.; Scudiero, D.; Selby, M.; Kobelt, D.; Lemm, M.; Fichtner, I.; Schlag, P.M.; Shoemaker, R.H.; Stein, U. Novel effect of antihelminthic Niclosamide on S100A4-mediated metastatic progression in colon cancer. J. Natl. Cancer Inst., 2011, 103(13), 1018-1036.
[http://dx.doi.org/10.1093/jnci/djr190] [PMID: 21685359]
[60]
Brown, D. Antibiotic resistance breakers: Can repurposed drugs fill the antibiotic discovery void? Nat. Rev. Drug Discov., 2015, 14(12), 821-832.
[http://dx.doi.org/10.1038/nrd4675] [PMID: 26493767]
[61]
Carlson-Banning, K.M.; Chou, A.; Liu, Z.; Hamill, R.J.; Song, Y.; Zechiedrich, L. Toward repurposing ciclopirox as an antibiotic against drug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae. PLoS One, 2013, 8(7), e69646.
[http://dx.doi.org/10.1371/journal.pone.0069646] [PMID: 23936064]
[62]
Yu, H.H.; Kim, K.J.; Cha, J.D.; Kim, H.K.; Lee, Y.E.; Choi, N.Y.; You, Y.O. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J. Med. Food, 2005, 8(4), 454-461.
[http://dx.doi.org/10.1089/jmf.2005.8.454] [PMID: 16379555]
[63]
Kim, S.H.; Shin, D.S.; Oh, M.N.; Chung, S.C.; Lee, J.S.; Oh, K.B. Inhibition of the bacterial surface protein anchoring transpeptidase sortase by isoquinoline alkaloids. Biosci. Biotechnol. Biochem., 2004, 68(2), 421-424.
[http://dx.doi.org/10.1271/bbb.68.421] [PMID: 14981307]
[64]
Sardana, D.; Zhu, C.; Zhang, M.; Gudivada, R.C.; Yang, L.; Jegga, A.G. Drug repositioning for orphan diseases. Brief. Bioinform., 2011, 12(4), 346-356.
[http://dx.doi.org/10.1093/bib/bbr021] [PMID: 21504985]
[65]
Xu, K.; Coté, T.R. Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases. Brief. Bioinform., 2011, 12(4), 341-345.
[http://dx.doi.org/10.1093/bib/bbr006] [PMID: 21357612]
[66]
Aguila, E.J.T.; Cua, I.H.Y. Repurposed GI drugs in the treatment of COVID-19. Dig. Dis. Sci., 2020, 65(8), 2452-2453.
[http://dx.doi.org/10.1007/s10620-020-06430-z] [PMID: 32601778]
[67]
Search of COVID-19 - List Results - ClinicalTrials.gov; , 2022. Available from https://clinicaltrials.gov/ct2/results?cond=COVID-19
[68]
Ng, Y.L.; Salim, C.K.; Chu, J.J.H. Drug repurposing for COVID-19: Approaches, challenges and promising candidates. Pharmacol. Ther., 2021, 228, 107930.
[http://dx.doi.org/10.1016/j.pharmthera.2021.107930] [PMID: 34174275]
[69]
Huang, D.; Yu, H.; Wang, T.; Yang, H.; Yao, R.; Liang, Z. Efficacy and safety of umifenovir for coronavirus disease 2019 (COVID 19): A systematic review and meta analysis. J. Med. Virol., 2021, 93(1), 481-490.
[http://dx.doi.org/10.1002/jmv.26256] [PMID: 32617989]
[70]
Musarrat, F.; Chouljenko, V.; Dahal, A.; Nabi, R.; Chouljenko, T.; Jois, S.D.; Kousoulas, K.G. The anti HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV 2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID 19 infections. J. Med. Virol., 2020, 92(10), 2087-2095.
[http://dx.doi.org/10.1002/jmv.25985] [PMID: 32374457]
[71]
Bobrowski, T.; Chen, L.; Eastman, R.T.; Itkin, Z.; Shinn, P.; Chen, C.; Guo, H.; Zheng, W.; Michael, S.; Simeonov, A.; Hall, M.D. Discovery of synergistic and antagonistic drug combinations against SARS-CoV-2 in vitro. BioRxiv, 2020.
[72]
Bronte, V.; Ugel, S.; Tinazzi, E.; Vella, A.; De Sanctis, F.; Canè, S.; Batani, V.; Trovato, R.; Fiore, A.; Petrova, V.; Hofer, F.; Barouni, R.M.; Musiu, C.; Caligola, S.; Pinton, L.; Torroni, L.; Polati, E.; Donadello, K.; Friso, S.; Pizzolo, F.; Iezzi, M.; Facciotti, F.; Pelicci, P.G.; Righetti, D.; Bazzoni, P.; Rampudda, M.; Comel, A.; Mosaner, W.; Lunardi, C.; Olivieri, O. Baricitinib restrains the immune dysregulation in patients with severe COVID-19. J. Clin. Invest., 2020, 130(12), 6409-6416.
[http://dx.doi.org/10.1172/JCI141772] [PMID: 32809969]
[73]
Cortegiani, A.; Ingoglia, G.; Ippolito, M.; Giarratano, A.; Einav, S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J. Crit. Care, 2020, 57, 279-283.
[http://dx.doi.org/10.1016/j.jcrc.2020.03.005] [PMID: 32173110]
[74]
Emadi, A.; Chua, J.V.; Talwani, R.; Bentzen, S.M.; Baddley, J. Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial. Trials, 2020, 21(1), 897.
[http://dx.doi.org/10.1186/s13063-020-04819-9] [PMID: 33115543]
[75]
Li, G.; Yuan, M.; Li, H.; Deng, C.; Wang, Q.; Tang, Y.; Zhang, H.; Yu, W.; Xu, Q.; Zou, Y.; Yuan, Y.; Guo, J.; Jin, C.; Guan, X.; Xie, F.; Song, J. Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: An open-label, non-randomised and controlled trial. Int. J. Antimicrob. Agents, 2021, 57(1), 106216.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.106216] [PMID: 33152450]
[76]
Sanchis-Gomar, F.; Lavie, C.J.; Morin, D.P.; Perez-Quilis, C.; Laukkanen, J.A.; Perez, M.V. Amiodarone in the COVID-19 era: treatment for symptomatic patients only, or drug to prevent infection? Am. J. Cardiovasc. Drugs, 2020, 20(5), 413-418.
[http://dx.doi.org/10.1007/s40256-020-00429-7] [PMID: 32737841]
[77]
Sinha, N.; Balayla, G. Hydroxychloroquine and COVID-19. Postgrad. Med. J., 2020, 96(1139), 550-555.
[http://dx.doi.org/10.1136/postgradmedj-2020-137785] [PMID: 32295814]
[78]
Stip, E. Psychiatry and COVID-19: The role of chlorpromazine. Can. J. Psychiatry, 2020, 65(10), 739-740.
[http://dx.doi.org/10.1177/0706743720934997] [PMID: 32536208]
[79]
Mahase, E. Covid-19: FDA authorises neutralising antibody bamlanivimab for non-admitted patients. BMJ, 2020, 371, m4362.
[http://dx.doi.org/10.1136/bmj.m4362] [PMID: 33177042]
[80]
Cadegiani, F.A. Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension? Am. J. Physiol. Endocrinol. Metab., 2020, 318(5), E587-E588.
[http://dx.doi.org/10.1152/ajpendo.00136.2020] [PMID: 32297520]
[81]
Sarohan, A.R. COVID-19: Endogenous retinoic acid theory and retinoic acid depletion syndrome. Med. Hypotheses, 2020, 144, 110250.
[http://dx.doi.org/10.1016/j.mehy.2020.110250] [PMID: 33254555]
[82]
Seeland, U.; Coluzzi, F.; Simmaco, M.; Mura, C.; Bourne, P.E.; Heiland, M.; Preissner, R.; Preissner, S. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. BMC Med., 2020, 18(1), 369.
[http://dx.doi.org/10.1186/s12916-020-01851-z] [PMID: 33234138]
[83]
Sinha, S.; Cheng, K.; Schäffer, A.A.; Aldape, K.; Schiff, E.; Ruppin, E. In vitro and in vivo identification of clinically approved drugs that modifyACE 2 expression. Mol. Syst. Biol., 2020, 16(7), e9628.
[http://dx.doi.org/10.15252/msb.20209628] [PMID: 32729248]
[84]
Hoffmann, M.; Hofmann-Winkler, H.; Smith, J.C.; Krüger, N.; Arora, P.; Sørensen, L.K.; Søgaard, O.S.; Hasselstrøm, J.B.; Winkler, M.; Hempel, T.; Raich, L.; Olsson, S.; Danov, O.; Jonigk, D.; Yamazoe, T.; Yamatsuta, K.; Mizuno, H.; Ludwig, S.; Noé, F.; Kjolby, M.; Braun, A.; Sheltzer, J.M.; Pöhlmann, S. Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity. EBioMedicine, 2021, 65, 103255.
[http://dx.doi.org/10.1016/j.ebiom.2021.103255] [PMID: 33676899]
[85]
M, P.; Reddy, G.J.; Hema, K.; Dodoala, S.; Koganti, B. Unravelling high-affinity binding compounds towards transmembrane protease serine 2 enzyme in treating SARS-CoV-2 infection using molecular modelling and docking studies. Eur. J. Pharmacol., 2021, 890, 173688.
[http://dx.doi.org/10.1016/j.ejphar.2020.173688] [PMID: 33130280]
[86]
Olaleye, O.A.; Kaur, M.; Onyenaka, C.C. Ambroxol hydrochloride inhibits the interaction between severe acute respiratory syndrome coronavirus 2 spike protein’s receptor binding domain and recombinant human ACE2. BioRxiv, 2020.
[http://dx.doi.org/10.1101/2020.09.13.295691]
[87]
Eslami, G.; Mousaviasl, S.; Radmanesh, E.; Jelvay, S.; Bitaraf, S.; Simmons, B.; Wentzel, H.; Hill, A.; Sadeghi, A.; Freeman, J.; Salmanzadeh, S.; Esmaeilian, H.; Mobarak, M.; Tabibi, R.; Jafari Kashi, A.H.; Lotfi, Z.; Talebzadeh, S.M.; Wickramatillake, A.; Momtazan, M.; Hajizadeh Farsani, M.; Marjani, S.; Mobarak, S. The impact of sofosbuvir/daclatasvir or ribavirin in patients with severe COVID-19. J. Antimicrob. Chemother., 2020, 75(11), 3366-3372.
[http://dx.doi.org/10.1093/jac/dkaa331] [PMID: 32812051]
[88]
Tan, Q.; Duan, L.; Ma, Y.; Wu, F.; Huang, Q.; Mao, K.; Xiao, W.; Xia, H.; Zhang, S.; Zhou, E.; Ma, P.; Song, S.; Li, Y.; Zhao, Z.; Sun, Y.; Li, Z.; Geng, W.; Yin, Z.; Jin, Y. Is oseltamivir suitable for fighting against COVID-19: In silico assessment, in vitro and retrospective study. Bioorg. Chem., 2020, 104, 104257.
[http://dx.doi.org/10.1016/j.bioorg.2020.104257] [PMID: 32927129]
[89]
Elfiky, A.A. Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp): A molecular docking study. Life Sci., 2020, 253, 117592.
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[90]
Rafi, M.O.; Bhattacharje, G.; Al-Khafaji, K. Combination of QSAR, molecular docking, molecular dynamic simulation and MM-PBSA: analogues of lopinavir and favipiravir as potential drug candidates against COVID-19. J. Biomol. Struct. Dyn., 2020, 1-20.
[PMID: 33251975]
[91]
Chen, H.; Zhang, Z.; Wang, L.; Huang, Z.; Gong, F.; Li, X.; Chen, Y.; Wu, J.J. First clinical study using HCV protease inhibitor danoprevir to treat COVID-19 patients. Medicine , 2020, 99(48), e23357.
[http://dx.doi.org/10.1097/MD.0000000000023357] [PMID: 33235105]
[92]
Mahdi, M.; Mótyán, J.A.; Szojka, Z.I.; Golda, M.; Miczi, M. Tőzsér, J. Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2s main protease. Virol. J., 2020, 17(1), 190.
[http://dx.doi.org/10.1186/s12985-020-01457-0] [PMID: 31906972]
[93]
Lin, M.H.; Moses, D.C.; Hsieh, C.H.; Cheng, S.C.; Chen, Y.H.; Sun, C.Y.; Chou, C.Y. Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res., 2018, 150, 155-163.
[http://dx.doi.org/10.1016/j.antiviral.2017.12.015] [PMID: 29289665]
[94]
Samimagham, H.R.; Hassani Azad, M.; Haddad, M.; Arabi, M.; Hooshyar, D. KazemiJahromi, M. The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial. Trials, 2020, 21(1), 848.
[http://dx.doi.org/10.1186/s13063-020-04773-6] [PMID: 31898511]
[95]
Wu, D.; Yang, X.O. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J. Microbiol. Immunol. Infect., 2020, 53(3), 368-370.
[http://dx.doi.org/10.1016/j.jmii.2020.03.005] [PMID: 32205092]
[96]
Cure, E.; Cumhur Cure, M. Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis. Diabetes Metab. Syndr., 2020, 14(4), 405-406.
[http://dx.doi.org/10.1016/j.dsx.2020.04.024] [PMID: 32335366]
[97]
Papapanou, M.; Papoutsi, E.; Giannakas, T.; Katsaounou, P. Plitidepsin: Mechanisms and clinical profile of a promising antiviral agent against COVID-19. J. Pers. Med., 2021, 11(7), 668-677.
[http://dx.doi.org/10.3390/jpm11070668] [PMID: 34357135]
[98]
Martins-Filho, P.R.; Barreto-Alves, J.A.; Fakhouri, R. Potential role for nitazoxanide in treating SARS-CoV-2 infection. Am. J. Physiol. Lung Cell. Mol. Physiol., 2020, 319(1), L35-L36.
[http://dx.doi.org/10.1152/ajplung.00170.2020] [PMID: 33496642]
[99]
Shim, J.S.; Liu, J.O. Recent advances in drug repositioning for the discovery of new anticancer drugs. Int. J. Biol. Sci., 2014, 10(7), 654-663.
[http://dx.doi.org/10.7150/ijbs.9224] [PMID: 25013375]
[100]
Matthews, S.J.; McCoy, C. Thalidomide: A review of approved and investigational uses. Clin. Ther., 2003, 25(2), 342-395.
[http://dx.doi.org/10.1016/S0149-2918(03)80085-1] [PMID: 12749503]
[101]
Oprea, T.I.; Mestres, J. Drug repurposing: far beyond new targets for old drugs. AAPS J., 2012, 14(4), 759-763.
[http://dx.doi.org/10.1208/s12248-012-9390-1] [PMID: 22826034]
[102]
Polamreddy, P.; Gattu, N. The drug repurposing landscape from 2012 to 2017: Evolution, challenges, and possible solutions. Drug Discov. Today, 2019, 24(3), 789-795.
[http://dx.doi.org/10.1016/j.drudis.2018.11.022] [PMID: 30513339]
[103]
Breckenridge, A.; Jacob, R. Overcoming the legal and regulatory barriers to drug repurposing. Nat. Rev. Drug Discov., 2019, 18(1), 1-2.
[http://dx.doi.org/10.1038/nrd.2018.92] [PMID: 29880920]
[104]
Mohapatra, T.K.; Subudhi, B.B. Repurposing of aspirin: Opportunities and challenges. Res. J. Pharm. Technol., 2019, 12(4), 2037-2044.
[http://dx.doi.org/10.5958/0974-360X.2019.00337.8]
[105]
Vane, J.R. Inhibition of prostaglandin biosynthesis as the mechanism of action of aspirin-like drugs. Adv. Biosci., 2014, 9, 395-411.
[106]
Rothwell, P.M.; Wilson, M.; Elwin, C.E.; Norrving, B.; Algra, A.; Warlow, C.P.; Meade, T.W. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet, 2010, 376(9754), 1741-1750.
[http://dx.doi.org/10.1016/S0140-6736(10)61543-7] [PMID: 20970847]
[107]
Cavalla, D. Scientific commercial value of drug repurposing. In: Dudley, J.; Berliocchi, L., Eds. Drug Repositioning- Approaches and Applications for Neurotherapeutics, 1st ed, CRC Press, Taylor & Francis Group: Boca Raton, 2016, pp. 3-22.
[108]
Raje, N.; Anderson, K. Thalidomide-a revival story. N. Engl. J. Med., 1999, 341(21), 1606-1609.
[http://dx.doi.org/10.1056/NEJM199911183412110] [PMID: 10564693]
[109]
Jourdan, J.P.; Bureau, R.; Rochais, C.; Dallemagne, P. Drug repositioning: A brief overview. J. Pharm. Pharmacol., 2020, 72(9), 1145-1151.
[http://dx.doi.org/10.1111/jphp.13273] [PMID: 32301512]
[110]
Pantziarka, P.; Sukhatme, V.; Bouche, G.; Meheus, L.; Sukhatme, V.P. Repurposing Drugs in Oncology (ReDO)—itraconazole as an anti-cancer agent. E-cancer. Med. Sci., 2015, 9, 521.
[http://dx.doi.org/10.3332/ecancer.2015.521] [PMID: 25932045]
[111]
Kim, J.; Tang, J.Y.; Gong, R.; Kim, J.; Lee, J.J.; Clemons, K.V.; Chong, C.R.; Chang, K.S.; Fereshteh, M.; Gardner, D.; Reya, T.; Liu, J.O.; Epstein, E.H.; Stevens, D.A.; Beachy, P.A. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell, 2010, 17(4), 388-399.
[http://dx.doi.org/10.1016/j.ccr.2010.02.027] [PMID: 20385363]
[112]
Srivastav, A.; Dhorje, S.; Lavhate, P. In silico drug repurposing: An antifungal drug, itraconazole, repurposed as an anticancer agent using molecular docking. MGM J. Med. Sci., 2020, 7(3), 110-118.
[http://dx.doi.org/10.4103/mgmj.mgmj_31_20]

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