Generic placeholder image

Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Mini-Review Article

Computational Evidence Based Perspective on the Plausible Repositioning of Fluoroquinolones for COVID-19 Treatment

Author(s): Vikas Yadav*

Volume 18, Issue 6, 2022

Published on: 19 October, 2022

Page: [407 - 413] Pages: 7

DOI: 10.2174/1573409918666220909094645

Price: $65

Abstract

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a serious global healthcare crisis, so there is an emergence of identifying efficacious therapeutic options. In a setting where there is an unavailability of definitive medication along with the constant eruption of vaccine-related controversies, the drugrepositioning approach seems to be an ideal step for the management of COVID-19 patients. Fluoroquinolones (FQs) are commonly prescribed antibiotics for the treatment of genitourinary tract and upper respiratory tract infections, including severe community-acquired pneumonia. Research over the years has postulated multifaceted implications of FQs in various pathological conditions. Previously, it has been reported that few, but not all FQs, possess strong antiviral activity with an unknown mechanism of action. Herein, an interesting perspective is discussed on repositioning possibilities of FQs for the SARS-CoV-2 infections based on the recent in silico evidential support. Noteworthy, FQs possess immunomodulatory and bactericidal activity which could be valuable for patients dealing with COVID-19 related complications. Conclusively, the current perspective could pave the way to initiate pre-clinical testing of FQs against several strains of SARS-CoV-2.

Keywords: Anti-COVID-19, drug, SARS-CoV-2, Fluoroquinolones, Drug Repositioning, Drug Discovery

Next »
Graphical Abstract

[1]
Abdel-Aal, M.A.A.; Abdel-Aziz, S.A.; Shaykoon, M.S.A.; Abuo-Rahma, G.E.D.A. Towards anticancer fluoroquinolones: A review article. Arch. Pharm., 2019, 352(7), 1800376.
[http://dx.doi.org/10.1002/ardp.201800376] [PMID: 31215674]
[2]
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W.J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet, 2020, 395(10224), 565-574.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[3]
Petrosillo, N.; Viceconte, G.; Ergonul, O.; Ippolito, G.; Petersen, E. COVID-19, SARS and MERS: Are they closely related? Clin. Microbiol. Infect., 2020, 26(6), 729-734.
[http://dx.doi.org/10.1016/j.cmi.2020.03.026] [PMID: 32234451]
[4]
Robke, L.; Pont, B.L.; Bongard, J.; Wurzer, S.; Smietana, K.; Moss, R. Impact of COVID-19 on pharmaceutical external innovation sourcing. Nat. Rev. Drug Discov., 2020, 19(12), 829.
[http://dx.doi.org/10.1038/d41573-020-00184-z] [PMID: 33173230]
[5]
Yadav, V.; Safari, R. Recent Patent based perspective on diagnostic and therapeutic interventions in malignant mesothelioma: Is drug repositioning knocking on the door? Rec. Patents Anticancer Drug Discov, 2021, 16(2), 187-203.
[http://dx.doi.org/10.2174/1574892816666210712113739] [PMID: 34254929]
[6]
Serafin, M.B.; Bottega, A.; Foletto, V.S.; da Rosa, T.F.; Hörner, A.; Hörner, R. Drug repositioning is an alternative for the treatment of coronavirus COVID-19. Int. J. Antimicrob. Agents, 2020, 55(6), 105969.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105969] [PMID: 32278811]
[7]
Palve, V.; Liao, Y.; Remsing Rix, L.L.; Rix, U. Turning liabilities into opportunities: Off-target based drug repurposing in cancer. Semin. Cancer Biol., 2021, 68, 209-229.
[http://dx.doi.org/10.1016/j.semcancer.2020.02.003] [PMID: 32044472]
[8]
Sultana, J.; Crisafulli, S.; Gabbay, F.; Lynn, E.; Shakir, S.; Trifirò, G. Challenges for drug repurposing in the COVID-19 pandemic era. Front. Pharmacol., 2020, 11, 588654.
[http://dx.doi.org/10.3389/fphar.2020.588654] [PMID: 33240091]
[9]
Pham, T.D.M.; Ziora, Z.M.; Blaskovich, M.A.T. Quinolone antibiotics. MedChemComm, 2019, 10(10), 1719-1739.
[http://dx.doi.org/10.1039/C9MD00120D] [PMID: 31803393]
[10]
Sharma, P.C.; Goyal, R.; Sharma, A.; Sharma, D.; Saini, N.; Rajak, H.; Sharma, S.; Thakur, V.K. Insights on fluoroquinolones in cancer therapy: Chemistry and recent developments. Mater. Today Chem., 2020, 17(10), 100296.
[http://dx.doi.org/10.1016/j.mtchem.2020.100296]
[11]
Yadav, V.; Talwar, P. Repositioning of fluoroquinolones from antibiotic to anti-cancer agents: An underestimated truth. Biomed. Pharmacother., 2019, 111, 934-946.
[http://dx.doi.org/10.1016/j.biopha.2018.12.119] [PMID: 30841473]
[12]
Molnar, D.M.; Kremzner, M.E. Fluoroquinolones: A hot topic for pharmacists and the food and drug administration’s division of drug information. J. Am. Pharm. Assoc., 2019, 59(1), 13-16.
[http://dx.doi.org/10.1016/j.japh.2018.08.011] [PMID: 30348510]
[13]
Khan, I.A.; Siddiqui, S.; Rehmani, S.; Kazmi, S.U.; Ali, S.H. Fluoroquinolones inhibit HCV by targeting its helicase. Antivir. Ther., 2012, 17(3), 467-476.
[http://dx.doi.org/10.3851/IMP1937] [PMID: 22293206]
[14]
Scroggs, S.L.P.; Andrade, C.C.; Chinnasamy, R.; Azar, S.R.; Schirtzinger, E.E.; Garcia, E.I.; Arterburn, J.B.; Hanley, K.A.; Rossi, S.L. Old drugs with new tricks: Efficacy of fluoroquinolones to suppress replication of flaviviruses. Viruses, 2020, 12(9), 1022.
[http://dx.doi.org/10.3390/v12091022] [PMID: 32933138]
[15]
Yamaya, M.; Nishimura, H.; Hatachi, Y.; Yasuda, H.; Deng, X.; Sasaki, T.; Mizuta, K.; Kubo, H.; Nagatomi, R. Levofloxacin inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells. Antimicrob. Agents Chemother., 2012, 56(8), 4052-4061.
[http://dx.doi.org/10.1128/AAC.00259-12] [PMID: 22585227]
[16]
Xu, Y.P.; Qiu, Y.; Zhang, B.; Chen, G.; Chen, Q.; Wang, M.; Mo, F.; Xu, J.; Wu, J.; Zhang, R.R.; Cheng, M.L.; Zhang, N.N.; Lyu, B.; Zhu, W.L.; Wu, M.H.; Ye, Q.; Zhang, D.; Man, J.H.; Li, X.F.; Cui, J.; Xu, Z.; Hu, B.; Zhou, X.; Qin, C.F. Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids. Cell Res., 2019, 29(4), 265-273.
[http://dx.doi.org/10.1038/s41422-019-0152-9] [PMID: 30814679]
[17]
Assar, S.; Nosratabadi, R.; Khorramdel Azad, H.; Masoumi, J.; Mohamadi, M.; Hassanshahi, G. A review of immunomodulatory effects of fluoroquinolones. Immunol. Invest., 2021, 50(8), 1007-1026.
[http://dx.doi.org/10.1080/08820139.2020.1797778] [PMID: 32746743]
[18]
Dalhoff, A. Immunomodulatory activities of fluoroquinolones. Infection, 2005, 33(S2), 55-70.
[http://dx.doi.org/10.1007/s15010-005-8209-8] [PMID: 16518713]
[19]
V’kovski, P.; Kratzel, A.; Steiner, S.; Stalder, H.; Thiel, V. Coronavirus biology and replication: Implications for SARS-CoV-2. Nat. Rev. Microbiol., 2021, 19(3), 155-170.
[http://dx.doi.org/10.1038/s41579-020-00468-6] [PMID: 33116300]
[20]
Sun, P.; Lu, X.; Xu, C.; Sun, W.; Pan, B. Understanding of COVID-19 based on current evidence. J. Med. Virol., 2020, 92(6), 548-551.
[http://dx.doi.org/10.1002/jmv.25722] [PMID: 32096567]
[21]
Anand, K.; Ziebuhr, J.; Wadhwani, P.; Mesters, J.R.; Hilgenfeld, R. Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science, 2003, 300(5626), 1763-1767.
[http://dx.doi.org/10.1126/science.1085658] [PMID: 12746549]
[22]
Dai, W.; Zhang, B.; Jiang, X.M.; Su, H.; Li, J.; Zhao, Y.; Xie, X.; Jin, Z.; Peng, J.; Liu, F.; Li, C.; Li, Y.; Bai, F.; Wang, H.; Cheng, X.; Cen, X.; Hu, S.; Yang, X.; Wang, J.; Liu, X.; Xiao, G.; Jiang, H.; Rao, Z.; Zhang, L.K.; Xu, Y.; Yang, H.; Liu, H. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 2020, 368(6497), 1331-1335.
[http://dx.doi.org/10.1126/science.abb4489] [PMID: 32321856]
[23]
Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 2020, 368(6489), 409-412.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
[24]
Chandel, V.; Sharma, P.P.; Raj, S.; Choudhari, R.; Rathi, B.; Kumar, D. Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2. J. Biomol. Struct. Dyn., 2022, 40(1), 249-262.
[http://dx.doi.org/10.1080/07391102.2020.1811773] [PMID: 32838660]
[25]
Pantsar, T.; Poso, A. Binding affinity via docking: Fact and fiction. Molecules, 2018, 23(8), 1899.
[http://dx.doi.org/10.3390/molecules23081899] [PMID: 30061498]
[26]
Marciniec, K.; Beberok, A.; Pęcak, P.; Boryczka, S.; Wrześniok, D. Ciprofloxacin and moxifloxacin could interact with SARS-CoV-2 protease: Preliminary in silico analysis. Pharmacol. Rep., 2020, 72(6), 1553-1561.
[http://dx.doi.org/10.1007/s43440-020-00169-0] [PMID: 33063271]
[27]
Foroumadi, A.; Emami, S.; Rajabalian, S.; Badinloo, M.; Mohammadhosseini, N.; Shafiee, A. N-Substituted piperazinyl quinolones as potential cytotoxic agents: Structure–activity relationships study. Biomed. Pharmacother., 2009, 63(3), 216-220.
[http://dx.doi.org/10.1016/j.biopha.2008.01.016] [PMID: 18328669]
[28]
Alaaeldin, R.; Mustafa, M.; Abuo-Rahma, G.E.D.A.; Fathy, M. In vitro inhibition and molecular docking of a new ciprofloxacin-chalcone against SARS-CoV-2 main protease. Fundam. Clin. Pharmacol., 2022, 36(1), 160-170.
[http://dx.doi.org/10.1111/fcp.12708] [PMID: 34268806]
[29]
Steuber, H.; Hilgenfeld, R. Recent advances in targeting viral proteases for the discovery of novel antivirals. Curr. Top. Med. Chem., 2010, 10(3), 323-345.
[http://dx.doi.org/10.2174/156802610790725470] [PMID: 20166951]
[30]
Agbowuro, A.A.; Huston, W.M.; Gamble, A.B.; Tyndall, J.D.A. Proteases and protease inhibitors in infectious diseases. Med. Res. Rev., 2018, 38(4), 1295-1331.
[http://dx.doi.org/10.1002/med.21475] [PMID: 29149530]
[31]
Schultze, J.L.; Aschenbrenner, A.C. COVID-19 and the human innate immune system. Cell, 2021, 184(7), 1671-1692.
[http://dx.doi.org/10.1016/j.cell.2021.02.029] [PMID: 33743212]
[32]
de la Rica, R.; Borges, M.; Gonzalez-Freire, M. COVID-19: In the eye of the cytokine storm. Front. Immunol., 2020, 11, 558898.
[http://dx.doi.org/10.3389/fimmu.2020.558898] [PMID: 33072097]
[33]
Hammond, S.M.; Caudy, A.A.; Hannon, G.J. Post-transcriptional gene silencing by double-stranded RNA. Nat. Rev. Genet., 2001, 2(2), 110-119.
[http://dx.doi.org/10.1038/35052556] [PMID: 11253050]
[34]
Uludağ, H.; Parent, K.; Aliabadi, H.M.; Haddadi, A. Prospects for RNAi therapy of COVID-19. Front. Bioeng. Biotechnol., 2020, 8, 916.
[http://dx.doi.org/10.3389/fbioe.2020.00916] [PMID: 32850752]
[35]
Csorba, T.; Kontra, L.; Burgyán, J. viral silencing suppressors: Tools forged to fine-tune host-pathogen coexistence. Virology, 2015, 479-480, 85-103.
[http://dx.doi.org/10.1016/j.virol.2015.02.028] [PMID: 25766638]
[36]
Ahmadi, A.; Moradi, S. In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection. Sci. Rep., 2021, 11(1), 10271.
[http://dx.doi.org/10.1038/s41598-021-89605-6] [PMID: 33986351]
[37]
Felicetti, T.; Cecchetti, V.; Manfroni, G. Modulating microRNA processing: Enoxacin, the progenitor of a new class of drugs. J. Med. Chem., 2020, 63(21), 12275-12289.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00510] [PMID: 32672457]
[38]
Farr, R.J.; Rootes, C.L.; Rowntree, L.C.; Nguyen, T.H.O.; Hensen, L.; Kedzierski, L.; Cheng, A.C.; Kedzierska, K.; Au, G.G.; Marsh, G.A.; Vasan, S.S.; Foo, C.H.; Cowled, C.; Stewart, C.R. Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection. PLoS Pathog., 2021, 17(7), e1009759.
[http://dx.doi.org/10.1371/journal.ppat.1009759] [PMID: 34320031]
[39]
Ardekani, A.M.; Naeini, M.M. The role of microRNAs in human diseases. Avicenna J. Med. Biotechnol., 2010, 2(4), 161-179.
[PMID: 23407304]
[40]
Bartoszewski, R.; Dabrowski, M.; Jakiela, B.; Matalon, S.; Harrod, K.S.; Sanak, M.; Collawn, J.F. SARS-CoV-2 may regulate cellular responses through depletion of specific host miRNAs. Am. J. Physiol. Lung Cell. Mol. Physiol., 2020, 319(3), L444-L455.
[http://dx.doi.org/10.1152/ajplung.00252.2020] [PMID: 32755307]
[41]
Ahmed, S.S.S.J.; Paramasivam, P.; Raj, K.; Kumar, V.; Murugesan, R.; Ramakrishnan, V. Regulatory cross talk between SARS-CoV-2 receptor binding and replication machinery in the human host. Front. Physiol., 2020, 11, 802.
[http://dx.doi.org/10.3389/fphys.2020.00802] [PMID: 32695025]
[42]
Romano, M.; Ruggiero, A.; Squeglia, F.; Maga, G.; Berisio, R. A structural view of SARS-CoV-2 RNA replication machinery: RNA synthesis, proofreading and final capping. Cells, 2020, 9(5), 1267.
[http://dx.doi.org/10.3390/cells9051267] [PMID: 32443810]
[43]
Ramos, F.D.; Carrasco, M.; Doyle, T.; Brierley, I. Programmed −1 ribosomal frameshifting in the SARS coronavirus. Biochem. Soc. Trans., 2004, 32(6), 1081-1083.
[http://dx.doi.org/10.1042/BST0321081] [PMID: 15506971]
[44]
Kelly, J.A.; Woodside, M.T.; Dinman, J.D. Programmed −1 ribosomal frameshifting in coronaviruses: A therapeutic target. Virology, 2021, 554, 75-82.
[http://dx.doi.org/10.1016/j.virol.2020.12.010] [PMID: 33387787]
[45]
Sun, Y.; Abriola, L.; Niederer, R.O.; Pedersen, S.F.; Alfajaro, M.M.; Silva Monteiro, V.; Wilen, C.B.; Ho, Y.C.; Gilbert, W.V.; Surovtseva, Y.V.; Lindenbach, B.D.; Guo, J.U. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting. Proc. Natl. Acad. Sci., 2021, 118(26), e2023051118.
[http://dx.doi.org/10.1073/pnas.2023051118] [PMID: 34185680]
[46]
Callaway, E. Delta coronavirus variant: Scientists brace for impact. Nature, 2021, 595(7865), 17-18.
[http://dx.doi.org/10.1038/d41586-021-01696-3] [PMID: 34158664]
[47]
Mohapatra, R.K.; Sarangi, A.K.; Kandi, V.; Azam, M.; Tiwari, R.; Dhama, K. Omicron (B.1.1.529 variant of SARS-CoV-2); an emerging threat: Current global scenario. J. Med. Virol., 2022, 94(5), 1780-1783.
[http://dx.doi.org/10.1002/jmv.27561] [PMID: 34964506]
[48]
Srivastava, K.; Singh, M.K. Drug repurposing in COVID-19: A review with past, present and future. Metabolism Open, 2021, 12, 100121.
[http://dx.doi.org/10.1016/j.metop.2021.100121] [PMID: 34462734]
[49]
Rodrigues, L.; Bento Cunha, R.; Vassilevskaia, T.; Viveiros, M.; Cunha, C. Drug Repurposing for COVID-19: A review and a novel strategy to identify new targets and potential drug candidates. Molecules, 2022, 27(9), 2723.
[http://dx.doi.org/10.3390/molecules27092723] [PMID: 35566073]
[50]
Scroggs, S.L.P.; Offerdahl, D.K.; Flather, D.P.; Morris, C.N.; Kendall, B.L.; Broeckel, R.M.; Beare, P.A.; Bloom, M.E. Fluoroquinolone antibiotics exhibit low antiviral activity against SARS-CoV-2 and MERS-CoV. Viruses, 2020, 13(1), 8.
[http://dx.doi.org/10.3390/v13010008] [PMID: 33374514]
[51]
Yadav, V.; Varshney, P.; Sultana, S.; Yadav, J.; Saini, N. Moxifloxacin and ciprofloxacin induces S-phase arrest and augments apoptotic effects of cisplatin in human pancreatic cancer cells via ERK activation. BMC Cancer, 2015, 15(1), 581.
[http://dx.doi.org/10.1186/s12885-015-1560-y] [PMID: 26260159]
[52]
Beović, B.; Doušak, M.; Ferreira-Coimbra, J.; Nadrah, K.; Rubulotta, F.; Belliato, M.; Berger-Estilita, J.; Ayoade, F.; Rello, J.; Erdem, H. Antibiotic use in patients with COVID-19: A ‘snapshot’ infectious diseases international research initiative (ID-IRI) survey. J. Antimicrob. Chemother., 2020, 75(11), 3386-3390.
[http://dx.doi.org/10.1093/jac/dkaa326] [PMID: 32766706]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy