Repurposing Drugs for Viruses and Cancer: A Novel Drug Repositioning Strategy for COVID-19

Wong, Ka Heng; Lim, Chie-Min; Yip, Ashley Jia Wen; Farouk, Isra Ahmad; Zabidi, Nur Zawanah; Low, Zheng Yao; Lal, Sunil K.

doi:10.1007/978-981-19-5399-6_18

Ka Heng Wong⁴,
Chie-Min Lim⁴,
Ashley Jia Wen Yip⁴,
Isra Ahmad Farouk⁴,
Nur Zawanah Zabidi⁴,
Zheng Yao Low⁴ &
…
Sunil K. Lal^4,5

528 Accesses
1 Citations
3 Altmetric

Abstract

The high infection capacity and rapid mutations in coronavirus disease 2019 (COVID-19) has been no stranger to many. The etiological agent that contributed to this global health crisis is by no means the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 is characterized by an episode of immune fluctuations, followed by hyperactivation of inflammatory responses, known as the cytokine storm. The rapid progression of the COVID-19 pandemic calls for new and promising antiviral therapeutics. Repositioning anticancer drugs against the virus is very much explored due to the common similar pathways or targeting structures, opening new windows for many possibilities. As such, the repurposing of zidovudine for Friend leukemia virus and ouabain for Ebola virus are among the successful examples. Other potential FDA-approved anticancer drugs to be repositioned for COVID-19 include imatinib, saracatinib, and homoharringtonine, which have been studied for other coronaviruses in the past. Furthermore, current anticancer drugs like carmofur, carfilzomib, zotatifin, plitidepsin, and toremifene have gained interesting outcomes with respect to SARS-CoV-2. It is well recognized that to achieve viral replication, viruses antagonise or hijack host proteins and signaling pathways to gain productive infection, with SARS-CoV-2 indeed being no exception. This review aims to discuss the drug repositioning approaches concerning previously established anticancer drugs on viruses, especially on SARS-CoV-2. We accentuate this idea with specific examples of how potential anticancer inhibitors can effectively be used against SARS-CoV-2 as well as the limitations and future perspectives of drug repositioning.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Chapter: USD 29.95; Price excludes VAT (USA)

eBook: USD 169.00; Price excludes VAT (USA)

Softcover Book: USD 219.99; Price excludes VAT (USA)

Hardcover Book: USD 219.99; Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

Abu-Eid R, Ward FJ (2021) Targeting the PI3K/Akt/mTOR pathway: a therapeutic strategy in COVID-19 patients. Immunol Lett 240:1–8. https://doi.org/10.1016/j.imlet.2021.09.005
Article CAS Google Scholar
Aherfi S, Pradines B, Devaux C et al (2021) Drug repurposing against SARS-CoV-1, SARS-CoV-2 and MERS-CoV. Future Microbiol 16:1341–1370. https://doi.org/10.2217/fmb-2021-0019
Article CAS Google Scholar
Aldea M, Michot J-M, Danlos F-X et al (2021) Repurposing of anticancer drugs expands possibilities for antiviral and anti-inflammatory discovery in COVID-19. Cancer Discov 11:1336–1344. https://doi.org/10.1158/2159-8290.CD-21-0144
Article CAS Google Scholar
Allarakhia M (2013) Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases. DDDT 753. https://doi.org/10.2147/DDDT.S46289
Al-Mahtab M, Akbar SM, Huq AF et al (2021) Extraordinary survival benefits of severe and critical patients with COVID-19 by immune modulators: the outcome of a clinical trial in Bangladesh. Euroasian J Hepato-Gastroenterol 10:68–75. https://doi.org/10.5005/jp-journals-10018-1327
Article Google Scholar
Alonso-Álvarez S, Pardal E, Sánchez-Nieto D et al (2017) Plitidepsin: design, development, and potential place in therapy. DDDT 11:253–264. https://doi.org/10.2147/DDDT.S94165
Article Google Scholar
Amarelle L, Lecuona E (2018) The antiviral effects of Na, K-ATPase inhibition: a min ireview. Int J Mol Sci 19:2154. https://doi.org/10.3390/ijms19082154
Article CAS Google Scholar
Amarelle L, Katzen J, Shigemura M et al (2019) Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery. Am J Phys Lung Cell Mol Phys 316:L1094–L1106. https://doi.org/10.1152/ajplung.00173.2018
Article CAS Google Scholar
Andersen KG, Rambaut A, Lipkin WI et al (2020) The proximal origin of SARS-CoV-2. Nat Med 26:450–452. https://doi.org/10.1038/s41591-020-0820-9
Article CAS Google Scholar
Babé LM, Craik CS (1997) Viral proteases: evolution of diverse structural motifs to optimize function. Cell 91:427–430. https://doi.org/10.1016/S0092-8674(00)80426-2
Article Google Scholar
Banerjee S, Biehl A, Gadina M et al (2017) JAK–STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs 77:521–546. https://doi.org/10.1007/s40265-017-0701-9
Article CAS Google Scholar
Barratt S, Medford AR, Millar AB (2014) Vascular endothelial growth factor in acute lung injury and acute respiratory distress syndrome. Respiration 87:329–342. https://doi.org/10.1159/000356034
Article CAS Google Scholar
Burkard C, Verheije MH, Haagmans BL et al (2015) ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells. J Virol 89:4434–4448. https://doi.org/10.1128/JVI.03274-14
Article CAS Google Scholar
Cao X (2020) COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol 20:269–270. https://doi.org/10.1038/s41577-020-0308-3
Article CAS Google Scholar
Cao J, Forrest JC, Zhang X (2015) A screen of the NIH clinical collection small molecule library identifies potential anti-coronavirus drugs. Antivir Res 114:1–10. https://doi.org/10.1016/j.antiviral.2014.11.010
Article CAS Google Scholar
Chan K, Robert F, Oertlin C et al (2019) eIF4A supports an oncogenic translation program in pancreatic ductal adenocarcinoma. Nat Commun 10:5151. https://doi.org/10.1038/s41467-019-13086-5
Article CAS Google Scholar
Chow WA, Jiang C, Guan M (2009) Anti-HIV drugs for cancer therapeutics: back to the future? Lancet Oncol 10:61–71. https://doi.org/10.1016/S1470-2045(08)70334-6
Article CAS Google Scholar
Ciliberto G, Mancini R, Paggi MG (2020) Drug repurposing against COVID-19: focus on anticancer agents. J Exp Clin Cancer Res 39:86. https://doi.org/10.1186/s13046-020-01590-2
Article CAS Google Scholar
Clouser CL, Patterson SE, Mansky LM (2010) Exploiting drug repositioning for discovery of a novel HIV combination therapy. J Virol 84:9301–9309. https://doi.org/10.1128/JVI.01006-10
Article CAS Google Scholar
Coleman CM, Sisk JM, Mingo RM et al (2016) Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus fusion. J Virol 90:8924–8933. https://doi.org/10.1128/JVI.01429-16
Article CAS Google Scholar
Coux O, Tanaka K, Goldberg AL (1996) Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem 65:801–847. https://doi.org/10.1146/annurev.bi.65.070196.004101
Article CAS Google Scholar
Cui W, Yang K, Yang H (2020) Recent Progress in the drug development targeting SARS-CoV-2 Main protease as treatment for COVID-19. Front Mol Biosci 7:616341. https://doi.org/10.3389/fmolb.2020.616341
Article CAS Google Scholar
Dementiev A, Joachimiak A, Nguyen H et al (2019) Molecular mechanism of inhibition of acid ceramidase by Carmofur. J Med Chem 62:987–992. https://doi.org/10.1021/acs.jmedchem.8b01723
Article CAS Google Scholar
Dodson AW, Taylor TJ, Knipe DM, Coen DM (2007) Inhibitors of the sodium potassium ATPase that impair herpes simplex virus replication identified via a chemical screening approach. Virology 366:340–348. https://doi.org/10.1016/j.virol.2007.05.001
Article CAS Google Scholar
Dong X, Fu J, Yin X et al (2016) Emodin: a review of its pharmacology, toxicity and pharmacokinetics: Emodin: pharmacology, toxicity and pharmacokinetics. Phytother Res 30:1207–1218. https://doi.org/10.1002/ptr.5631
Article CAS Google Scholar
Dowall SD, Bewley K, Watson RJ et al (2016) Antiviral screening of multiple compounds against Ebola virus. Viruses 8:277. https://doi.org/10.3390/v8110277
Article Google Scholar
Dyall J, Coleman CM, Hart BJ et al (2014) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 58:4885–4893. https://doi.org/10.1128/AAC.03036-14
Article CAS Google Scholar
Dyall J, Gross R, Kindrachuk J et al (2017) Middle East respiratory syndrome and severe acute respiratory syndrome: current therapeutic options and potential targets for novel therapies. Drugs 77:1935–1966. https://doi.org/10.1007/s40265-017-0830-1
Article Google Scholar
El Bairi K, Trapani D, Petrillo A et al (2020) Repurposing anticancer drugs for the management of COVID-19. Eur J Cancer 141:40–61. https://doi.org/10.1016/j.ejca.2020.09.014
Article CAS Google Scholar
Eron JJ, Benoit SL, Jemsek J et al (1995) Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD⁴⁺ cells per cubic millimeter. N Engl J Med 333:1662–1669. https://doi.org/10.1056/NEJM199512213332502
Article CAS Google Scholar
Escalante CP, Zalpour A (2011) Vascular endothelial growth factor inhibitor-induced hypertension: basics for primary care providers. Cardiol Res Pract 2011:1–8. https://doi.org/10.4061/2011/816897
Article Google Scholar
Faletti L, Ehl S, Heeg M (2021) Germline STAT3 gain-of-function mutations in primary immunodeficiency: impact on the cellular and clinical phenotype. Biom J 44:412–421. https://doi.org/10.1016/j.bj.2021.03.003
Article CAS Google Scholar
Fattahi S, Khalifehzadeh-Esfahani Z, Mohammad-Rezaei M et al (2022) PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy. Immunol Res 70:269. https://doi.org/10.1007/s12026-022-09268-x
Article CAS Google Scholar
Fleming S (2016) Viral inhibition of the IFN-induced JAK/STAT signaling pathway: development of live attenuated vaccines by mutation of viral-encoded IFN-antagonists. Vaccine 4:23. https://doi.org/10.3390/vaccines4030023
Article CAS Google Scholar
García-Dorival I, Wu W, Dowall S et al (2014) Elucidation of the Ebola virus VP24 cellular Interactome and disruption of virus biology through targeted inhibition of host-cell protein function. J Proteome Res 13:5120–5135. https://doi.org/10.1021/pr500556d
Article CAS Google Scholar
Gerson-Gurwitz A, Young NP, Goel VK et al (2021) Zotatifin, an eIF4A-selective inhibitor, blocks tumor growth in receptor tyrosine kinase driven tumors. Front Oncol 11:766298. https://doi.org/10.3389/fonc.2021.766298
Article Google Scholar
Gordon DE, Jang GM, Bouhaddou M et al (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583:459–468. https://doi.org/10.1038/s41586-020-2286-9
Article CAS Google Scholar
Huang Y, Yang C, Xu X et al (2020) Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 41:1141–1149. https://doi.org/10.1038/s41401-020-0485-4
Article CAS Google Scholar
Jafarzadeh A, Nemati M, Jafarzadeh S (2021) Contribution of STAT3 to the pathogenesis of COVID-19. Microb Pathog 154:104836. https://doi.org/10.1016/j.micpath.2021.104836
Article CAS Google Scholar
Jarada TN, Rokne JG, Alhajj R (2020) A review of computational drug repositioning: strategies, approaches, opportunities, challenges, and directions. J Cheminform 12:46. https://doi.org/10.1186/s13321-020-00450-7
Article CAS Google Scholar
Jayaweera SPE, Wanigasinghe Kanakanamge SP, Rajalingam D, Silva GN (2021) Carfilzomib: a promising proteasome inhibitor for the treatment of relapsed and refractory multiple myeloma. Front Oncol 11:740796. https://doi.org/10.3389/fonc.2021.740796
Article Google Scholar
Jeon S, Ko M, Lee J et al (2020) Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. Antimicrob Agents Chemother 64:e00819–e00820. https://doi.org/10.1128/AAC.00819-20
Article CAS Google Scholar
Jin Z, Du X, Xu Y et al (2020a) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582:289–293. https://doi.org/10.1038/s41586-020-2223-y
Article CAS Google Scholar
Jin Z, Zhao Y, Sun Y et al (2020b) Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur. Nat Struct Mol Biol 27:529–532. https://doi.org/10.1038/s41594-020-0440-6
Article CAS Google Scholar
Johansen LM, Brannan JM, Delos SE et al (2013) FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Sci Transl Med 5:190ra79. https://doi.org/10.1126/scitranslmed.3005471
Article CAS Google Scholar
Johansson MA, Quandelacy TM, Kada S et al (2021) SARS-CoV-2 transmission from people without COVID-19 symptoms. JAMA Netw Open 4:e2035057. https://doi.org/10.1001/jamanetworkopen.2020.35057
Article Google Scholar
Jourdan J-P, Bureau R, Rochais C, Dallemagne P (2020) Drug repositioning: a brief overview. J Pharm Pharmacol 72:1145–1151. https://doi.org/10.1111/jphp.13273
Article CAS Google Scholar
Kaushik V, Azad N, Yakisich JS, Iyer AKV (2017) Antitumor effects of naturally occurring cardiac glycosides convallatoxin and peruvoside on human ER+ and triple-negative breast cancers. Cell Death Discov 3:1–9. https://doi.org/10.1038/cddiscovery.2017.9
Article CAS Google Scholar
Kepp O, Menger L, Vacchelli E et al (2012) Anticancer activity of cardiac glycosides. Oncoimmunology 1:1640–1642. https://doi.org/10.4161/onci.21684
Article Google Scholar
Khezri MR, Varzandeh R, Ghasemnejad-Berenji M (2022) The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy. Cell Mol Biol Lett 27:6. https://doi.org/10.1186/s11658-022-00308-w
Article CAS Google Scholar
Kim N, Yim HY, He N et al (2016) Cardiac glycosides display selective efficacy for STK11 mutant lung cancer. Sci Rep 6:29721. https://doi.org/10.1038/srep29721
Article CAS Google Scholar
Kong Y, Han J, Wu X et al (2020) VEGF-D: a novel biomarker for detection of COVID-19 progression. Crit Care 24:373. https://doi.org/10.1186/s13054-020-03079-y
Article Google Scholar
Kortuem KM, Stewart AK (2013) Carfilzomib. Blood 121:893–897. https://doi.org/10.1182/blood-2012-10-459883
Article CAS Google Scholar
Laird GM, Eisele EE, Rabi SA et al (2014) A novel cell-based high-throughput screen for inhibitors of HIV-1 gene expression and budding identifies the cardiac glycosides. J Antimicrob Chemother 69:988–994. https://doi.org/10.1093/jac/dkt471
Article CAS Google Scholar
Li X, Zhong X, Wang Y et al (2021) Clinical determinants of the severity of COVID-19: a systematic review and meta-analysis. PLoS One 16:e0250602. https://doi.org/10.1371/journal.pone.0250602
Article CAS Google Scholar
Low ZY, Yip AJW, Lal SK (2022, 1868) Repositioning Ivermectin for Covid-19 treatment: molecular mechanisms of action against SARS-CoV-2 replication. Biochim Biophys Acta (BBA): Mol Basis Dis:166294. https://doi.org/10.1016/j.bbadis.2021.166294
Low ZY, Farouk IA, Lal SK (2020) Drug repositioning: new approaches and future prospects for life-debilitating diseases and the COVID-19 pandemic outbreak. Viruses 12:1058. https://doi.org/10.3390/v12091058
Article CAS Google Scholar
Low ZY, Yip AJW, Sharma A, Lal SK (2021) SARS coronavirus outbreaks past and present—a comparative analysis of SARS-CoV-2 and its predecessors. Virus Genes 57:307–317. https://doi.org/10.1007/s11262-021-01846-9
Article CAS Google Scholar
Lü S, Wang J (2014) Homoharringtonine and omacetaxine for myeloid hematological malignancies. J Hematol Oncol 7:2. https://doi.org/10.1186/1756-8722-7-2
Article CAS Google Scholar
Ma X, Xie L, Wartchow C et al (2017) Structural basis for therapeutic inhibition of influenza a polymerase PB2 subunit. Sci Rep 7:9385. https://doi.org/10.1038/s41598-017-09538-x
Article CAS Google Scholar
Ma C, Hu Y, Townsend JA et al (2020) Ebselen, disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin are nonspecific promiscuous SARS-CoV-2 Main protease inhibitors. ACS Pharmacol Transl Sci 3:1265–1277. https://doi.org/10.1021/acsptsci.0c00130
Article CAS Google Scholar
Machitani M, Yasukawa M, Nakashima J et al (2020) RNA-dependent RNA polymerase, RdRP, a promising therapeutic target for cancer and potentially COVID-19. Cancer Sci 111:3976–3984. https://doi.org/10.1111/cas.14618
Article CAS Google Scholar
Mani D, Wadhwani A, Krishnamurthy PT (2019) Drug repurposing in antiviral research: a current scenario. JYP 11:117–121. https://doi.org/10.5530/jyp.2019.11.26
Article CAS Google Scholar
Mao C, Yang Z-Y, He B-F et al (2012) Toremifene versus tamoxifen for advanced breast cancer. Cochrane Database Syst Rev 2021:CD008926. https://doi.org/10.1002/14651858.CD008926.pub2
Article Google Scholar
Martin WR, Cheng F (2020) Repurposing of FDA-approved Toremifene to treat COVID-19 by blocking the spike glycoprotein and NSP14 of SARS-CoV-2. J Proteome Res 19:4670–4677. https://doi.org/10.1021/acs.jproteome.0c00397
Article CAS Google Scholar
Martinez MA (2021) Plitidepsin: a repurposed drug for the treatment of COVID-19. Antimicrob Agents Chemother 65:e00200–e00221. https://doi.org/10.1128/AAC.00200-21
Article CAS Google Scholar
Medford ARL (2006) Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm? Thorax 61:621–626. https://doi.org/10.1136/thx.2005.040204
Article CAS Google Scholar
Mengist HM, Dilnessa T, Jin T (2021) Structural basis of potential inhibitors targeting SARS-CoV-2 Main protease. Front Chem 9:622898. https://doi.org/10.3389/fchem.2021.622898
Article CAS Google Scholar
Montero H, Pérez-Gil G, Sampieri CL (2019) Eukaryotic initiation factor 4A (eIF4A) during viral infections. Virus Genes 55:267–273. https://doi.org/10.1007/s11262-019-01641-7
Article CAS Google Scholar
Müller C, Obermann W, Karl N et al (2021) The rocaglate CR-31-B (−) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo. Antivir Res 186:105012. https://doi.org/10.1016/j.antiviral.2021.105012
Article CAS Google Scholar
Namba T, Kodama R, Moritomo S et al (2015) Zidovudine, an anti-viral drug, resensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine by inhibition of the Akt-GSK3β-snail pathway. Cell Death Dis 6:e1795–e1795. https://doi.org/10.1038/cddis.2015.172
Article CAS Google Scholar
Nebigil CG, Moog C, Vagner S et al (2020) Flavaglines as natural products targeting eIF4A and prohibitins: from traditional Chinese medicine to antiviral activity against coronaviruses. Eur J Med Chem 203:112653. https://doi.org/10.1016/j.ejmech.2020.112653
Article CAS Google Scholar
Neveu G, Barouch-Bentov R, Ziv-Av A et al (2012) Identification and targeting of an interaction between a tyrosine motif within hepatitis C virus Core protein and AP2M1 essential for viral assembly. PLoS Pathog 8:e1002845. https://doi.org/10.1371/journal.ppat.1002845
Article CAS Google Scholar
Obermann W, Friedrich A, Madhugiri R et al (2022) Rocaglates as antivirals: comparing the effects on viral resistance, anti-Coronaviral activity, RNA-clamping on eIF4A and immune cell toxicity. Viruses 14:519. https://doi.org/10.3390/v14030519
Article CAS Google Scholar
Oprea TI, Bauman JE, Bologa CG et al (2011) Drug repurposing from an academic perspective. Drug Discovery Today: Therapeutic Strategies 8:61–69. https://doi.org/10.1016/j.ddstr.2011.10.002
Article Google Scholar
Ostertag W, Roesler G, Krieg CJ et al (1974) Induction of endogenous virus and of thymidine kinase by Bromodeoxyuridine in cell cultures transformed by friend virus. Proc Natl Acad Sci 71:4980–4985. https://doi.org/10.1073/pnas.71.12.4980
Article CAS Google Scholar
Owen K, Brockwell N, Parker B (2019) JAK-STAT signaling: a double-edged sword of immune regulation and cancer progression. Cancers 11:2002. https://doi.org/10.3390/cancers11122002
Article CAS Google Scholar
Pang J, Xu F, Aondio G et al (2021) Efficacy and tolerability of bevacizumab in patients with severe Covid-19. Nat Commun 12:814. https://doi.org/10.1038/s41467-021-21085-8
Article CAS Google Scholar
Papapanou M, Papoutsi E, Giannakas T, Katsaounou P (2021) Plitidepsin: mechanisms and clinical profile of a promising antiviral agent against COVID-19. JPM 11:668. https://doi.org/10.3390/jpm11070668
Article Google Scholar
Parasher A (2021) COVID-19: current understanding of its pathophysiology, clinical presentation and treatment. Postgrad Med J 97:312–320. https://doi.org/10.1136/postgradmedj-2020-138577
Article Google Scholar
Patocka J, Kuca K, Oleksak P et al (2021) Rapamycin: drug repurposing in SARS-CoV-2 infection. Pharmaceuticals 14:217. https://doi.org/10.3390/ph14030217
Article CAS Google Scholar
Porta C, Paglino C, Mosca A (2014) Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol 4. https://doi.org/10.3389/fonc.2014.00064
Prudencio M, Mota M (2012) Targeting host factors to circumvent anti-malarial drug resistance. CPD 19:290–299. https://doi.org/10.2174/1381612811306020290
Article Google Scholar
PubChem (2022a) Imatinib. https://pubchem.ncbi.nlm.nih.gov/compound/5291. Accessed 3 Apr 2022
PubChem (2022b) Saracatinib. https://pubchem.ncbi.nlm.nih.gov/compound/10302451. Accessed 3 Apr 2022
PubChem (2022c) Homoharringtonine,(S). https://pubchem.ncbi.nlm.nih.gov/compound/16219462. Accessed 3 Apr 2022
Pushpakom S, Iorio F, Eyers PA et al (2019) Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18:41–58. https://doi.org/10.1038/nrd.2018.168
Article CAS Google Scholar
Queirós-Reis L, Gomes da Silva P, Gonçalves J et al (2021) SARS-CoV-2 virus−host interaction: currently available structures and implications of variant emergence on infectivity and immune response. IJMS 22:10836. https://doi.org/10.3390/ijms221910836
Article CAS Google Scholar
Sonia Ribeiro (2018) Data exclusivity, market protection, orphan and paediatric rewards
Google Scholar
Ritchie MD, Holzinger ER, Li R et al (2015) Methods of integrating data to uncover genotype–phenotype interactions. Nat Rev Genet 16:85–97. https://doi.org/10.1038/nrg3868
Article CAS Google Scholar
Rodriguez S, Hug C, Todorov P et al (2021) Machine learning identifies candidates for drug repurposing in Alzheimer’s disease. Nat Commun 12:1033. https://doi.org/10.1038/s41467-021-21330-0
Article CAS Google Scholar
Scanlon KJ, Kashani-Sabet M, Sowers LC (1989) Overexpression of DNA replication and repair enzymes in cisplatin-resistant human colon carcinoma HCT8 cells and circumvention by azidothymidine. Cancer Commun 1:269–275
CAS Google Scholar
Senapati S, Mahanta AK, Kumar S, Maiti P (2018) Controlled drug delivery vehicles for cancer treatment and their performance. Sig Transduct Target Ther 3:7. https://doi.org/10.1038/s41392-017-0004-3
Article CAS Google Scholar
Service RF (2021) A call to arms. Science 371:1092–1095. https://doi.org/10.1126/science.371.6534.1092
Article Google Scholar
Shereen MA, Khan S, Kazmi A et al (2020) COVID-19 infection: emergence, transmission, and characteristics of human coronaviruses. J Adv Res 24:91–98. https://doi.org/10.1016/j.jare.2020.03.005
Article CAS Google Scholar
Shin J, Jung E, Kim M et al (2018) Saracatinib inhibits Middle East respiratory syndrome-coronavirus replication in vitro. Viruses 10:283. https://doi.org/10.3390/v10060283
Article CAS Google Scholar
Siminea N, Popescu V, Sanchez Martin JA et al (2022) Network analytics for drug repurposing in COVID-19. Brief Bioinform 23:bbab490. https://doi.org/10.1093/bib/bbab490
Article CAS Google Scholar
Sun W, Sanderson PE, Zheng W (2016) Drug combination therapy increases successful drug repositioning. Drug Discov Today 21:1189–1195. https://doi.org/10.1016/j.drudis.2016.05.015
Article CAS Google Scholar
Talevi A, Bellera CL (2020) Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics. Expert Opin Drug Discovery 15:397–401. https://doi.org/10.1080/17460441.2020.1704729
Article Google Scholar
Taroncher-Oldenburg G, Müller C, Obermann W et al (2021) Targeting the DEAD-box RNA helicase eIF4A with Rocaglates—a pan-antiviral strategy for minimizing the impact of future RNA virus pandemics. Microorganisms 9:540. https://doi.org/10.3390/microorganisms9030540
Article CAS Google Scholar
Taschuk F, Cherry S (2020) DEAD-box helicases: sensors, regulators, and effectors for antiviral defense. Viruses 12:181. https://doi.org/10.3390/v12020181
Article CAS Google Scholar
Taylor K, Das S, Pearson M et al (2019) Systematic drug repurposing to enable precision medicine: a case study in breast cancer. Digit Med 5:180. https://doi.org/10.4103/digm.digm_28_19
Article Google Scholar
Thompson PA, Eam B, Young NP et al (2021) Targeting oncogene mRNA translation in B-cell malignancies with eFT226, a potent and selective inhibitor of eIF4A. Mol Cancer Ther 20:26–36. https://doi.org/10.1158/1535-7163.MCT-19-0973
Article CAS Google Scholar
Tomita K, Saito Y, Suzuki T et al (2020) Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury. Naunyn Schmiedeberg's Arch Pharmacol 393:2365–2374. https://doi.org/10.1007/s00210-020-01947-6
Article CAS Google Scholar
Vij R, Wang L, Orlowski RZ et al (2009) Carfilzomib (CFZ), a novel proteasome inhibitor for relapsed or refractory multiple myeloma, is associated with minimal peripheral neuropathic effects. Blood 114:430–430. https://doi.org/10.1182/blood.V114.22.430.430
Article Google Scholar
Vogel TP, Milner JD, Cooper MA (2015) The Ying and Yang of STAT3 in human disease. J Clin Immunol 35:615–623. https://doi.org/10.1007/s10875-015-0187-8
Article CAS Google Scholar
Wang J (2020) Fast identification of possible drug treatment of coronavirus Disease-19 (COVID-19) through computational drug repurposing study. J Chem Inf Model 60:3277–3286. https://doi.org/10.1021/acs.jcim.0c00179
Article CAS Google Scholar
Wang Y, Lv Z, Chu Y (2015) HIV protease inhibitors: a review of molecular selectivity and toxicity. HIV 95. https://doi.org/10.2147/HIV.S79956
Wang M-Y, Zhao R, Gao L-J et al (2020) SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front Cell Infect Microbiol 10:587269. https://doi.org/10.3389/fcimb.2020.587269
Article CAS Google Scholar
Waxman AJ, Clasen S, Hwang W-T et al (2018) Carfilzomib-associated cardiovascular adverse events: a systematic review and meta-analysis. JAMA Oncol 4:e174519. https://doi.org/10.1001/jamaoncol.2017.4519
Article Google Scholar
Wehbe Z, Hammoud S, Soudani N et al (2020) Molecular insights into SARS COV-2 interaction with cardiovascular disease: role of RAAS and MAPK signaling. Front Pharmacol 11
Google Scholar
White KM, Rosales R, Yildiz S et al (2021) Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science 371:926–931. https://doi.org/10.1126/science.abf4058
Article CAS Google Scholar
Wong RW, Balachandran A, Ostrowski MA, Cochrane A (2013) Digoxin suppresses HIV-1 replication by altering viral RNA processing. PLoS Pathog 9:e1003241. https://doi.org/10.1371/journal.ppat.1003241
Article CAS Google Scholar
Wong RW, Lingwood CA, Ostrowski MA et al (2018) Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling. Sci Rep 8:850. https://doi.org/10.1038/s41598-018-19298-x
Article CAS Google Scholar
World Health Organization (2022) Tracking SARS-CoV-2 variants. World Health Organization, In. https://www.who.int/health-topics/typhoid/tracking-SARS-CoV-2-variants. Accessed 29 Mar 2022
Google Scholar
Worldometer (2022) COVID live—coronavirus statistics—Worldometer. In: Worldometer. https://www.worldometers.info/coronavirus/. Accessed 30 Mar 2022
Wu D, Wu T, Liu Q, Yang Z (2020) The SARS-CoV-2 outbreak: what we know. Int J Infect Dis 94:44–48. https://doi.org/10.1016/j.ijid.2020.03.004
Article CAS Google Scholar
Yang J, Nie J, Ma X et al (2019) Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer 18:26. https://doi.org/10.1186/s12943-019-0954-x
Article Google Scholar
Yu H, Lee H, Herrmann A et al (2014) Revisiting STAT3 signaling in cancer: new and unexpected biological functions. Nat Rev Cancer 14:736–746. https://doi.org/10.1038/nrc3818
Article CAS Google Scholar
Zanella I, Zizioli D, Castelli F, Quiros-Roldan E (2021) Tenofovir, another inexpensive, well-known and widely available old drug repurposed for SARS-COV-2 infection. Pharmaceuticals 14:454. https://doi.org/10.3390/ph14050454
Article CAS Google Scholar
Zeng X, Zhu S, Liu X et al (2019) deepDR: a network-based deep learning approach to in silico drug repositioning. Bioinformatics 35:5191–5198. https://doi.org/10.1093/bioinformatics/btz418
Article CAS Google Scholar
Zhao Y, Ren J, Harlos K et al (2016) Toremifene interacts with and destabilizes the Ebola virus glycoprotein. Nature 535:169–172. https://doi.org/10.1038/nature18615
Article CAS Google Scholar
Zhou Y, Hou Y, Shen J et al (2020a) Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov 6:14. https://doi.org/10.1038/s41421-020-0153-3
Article CAS Google Scholar
Zhou Y, Wang F, Tang J et al (2020b) Artificial intelligence in COVID-19 drug repurposing. The Lancet Digital Health 2:e667–e676. https://doi.org/10.1016/S2589-7500(20)30192-8
Article Google Scholar
Zou S, Tong Q, Liu B et al (2020) Targeting STAT3 in cancer immunotherapy. Mol Cancer 19:145. https://doi.org/10.1186/s12943-020-01258-7
Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

School of Science, Monash University Malaysia, Subang Jaya, Selangor, Malaysia
Ka Heng Wong, Chie-Min Lim, Ashley Jia Wen Yip, Isra Ahmad Farouk, Nur Zawanah Zabidi, Zheng Yao Low & Sunil K. Lal
Tropical Medicine and Biology Platform, Monash University Malaysia, Subang Jaya, Selangor, Malaysia
Sunil K. Lal

Authors

Ka Heng Wong
View author publications
You can also search for this author in PubMed Google Scholar
Chie-Min Lim
View author publications
You can also search for this author in PubMed Google Scholar
Ashley Jia Wen Yip
View author publications
You can also search for this author in PubMed Google Scholar
Isra Ahmad Farouk
View author publications
You can also search for this author in PubMed Google Scholar
Nur Zawanah Zabidi
View author publications
You can also search for this author in PubMed Google Scholar
Zheng Yao Low
View author publications
You can also search for this author in PubMed Google Scholar
Sunil K. Lal
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sunil K. Lal .

Editor information

Editors and Affiliations

Department of Biotechnology, Panjab University, Chandigarh, Chandigarh, India
Ranbir Chander Sobti
School of Science, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
Sunil K. Lal
Delhi Pharmaceutical Sciences and Research, New Delhi, India
Ramesh K. Goyal

Ethics declarations

KHW, CML, AJWP, IAF, NZZ, and ZYL contributed equally to the preparation and drafting of the manuscript. Critical revisions, supervision and conceptualization of the article were done by SKL.

Conflict of Interest

All authors have read and agreed to the published version of the manuscript. All authors have declared that there is no conflict of interest.

Rights and permissions

Reprints and permissions

Copyright information

About this chapter

Cite this chapter

Wong, K.H. et al. (2023). Repurposing Drugs for Viruses and Cancer: A Novel Drug Repositioning Strategy for COVID-19. In: Sobti, R.C., Lal, S.K., Goyal, R.K. (eds) Drug Repurposing for Emerging Infectious Diseases and Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-19-5399-6_18

Download citation

DOI: https://doi.org/10.1007/978-981-19-5399-6_18
Published: 08 February 2023
Publisher Name: Springer, Singapore
Print ISBN: 978-981-19-5398-9
Online ISBN: 978-981-19-5399-6
eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics