Therapeutic Potential of Iron Chelators in Viral Diseases: A
Systematic Review

Maryam   Shamseddini   Lori; Azade   Kalantari   Khandani; Gholamreza      Dehghannoudeh; Mandana      Ohadi; Mehdi      Ansari

doi:10.2174/0109298673259596231211113211

Abstract

Background: Iron chelators (ICs) have recently emerged as one of the new methods of treatment for viral infections. This study aimed to evaluate the efficiency and safety of natural ICs compared to synthetic ICs. Natural and synthetic ICs are the most common therapeutic agents tested for the treatment of viral infections. When evaluated against synthetic ICs, natural ICs are probably favored owing to their lower toxicity and safer properties. The main objective of the present systematic review was to assess the current evidence on the role of pharmacological mechanisms in the treatment of viral infections.

Methods: This study was designed as a systematic review in which search strategies were focused on two electronic databases, PubMed, and Scopus, between 2017 and 2021. A search filter with two subjects, “iron chelators” and “viral infection”, was employed.

Results: According to the results, both natural and synthetic chelators had a considerable impact on the treatment of viral infections via various mechanisms, with natural ICs being the most extensively used.

Conclusion: Natural and synthetic ICs exert their effects through different pharmacological mechanisms. Among these compounds, natural chelators are more widely used due to their safety, efficacy, and a wider range of applications.

« Previous Next »

Mirza A.Z.; Shamshad H.; Osra F.A.; Habeebullah T.M.; Morad M.; An overview of viruses discovered over the last decades and drug development for the current pandemic. Eur J Pharmacol 2021,890,173746 10.1016/j.ejphar.2020.173746 33221318 Wu F.; Zhao S.; Yu B.; Chen Y.M.; Wang W.; Song Z.G.; Hu Y.; Tao Z.W.; Tian J.H.; Pei Y.Y.; Yuan M.L.; Zhang Y.L.; Dai F.H.; Liu Y.; Wang Q.M.; Zheng J.J.; Xu L.; Holmes E.C.; Zhang Y.Z.; A new coronavirus associated with human respiratory disease in China. Nature 2020,579(7798),265-269 10.1038/s41586-020-2008-3 32015508 WHO estimated that in 2019, approximately 290, 000 people died from hepatitis C 2019. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c#:~:text=WHO%20estimated%20that%20in%202019%2C%20approximately%20290%20000,is%20currently%20no%20effective%20vaccine%20against%20hepatitis%20C2019 In 2019, hepatitis B resulted in an estimated 820, 000 deaths. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b2019 Schmidt S.M.; The role of iron in viral infections. Front Biosci 2020,25(4),893-911 10.2741/4839 31585922 Aslam N.; Sarfaraz I.M.; Makhdoom H.S.; Rizwan M.; Naseer Q.U.A.; Afzal M.; Muneer R.; Batool F.; Effects of chelating agents on heavy metals in Hepatitis C Virus (HCV) patients. Math Biosci Eng 2019,16(3),1138-1149 10.3934/mbe.2019054 30947412 Meyer D.; Iron chelation as therapy for HIV and Mycobacterium tuberculosis co-infection under conditions of iron overload. Curr Pharm Des 2006,12(16),1943-1947 10.2174/138161206777442164 16787239 Hatcher H.C.; Singh R.N.; Torti F.M.; Torti S.V.; Synthetic and natural iron chelators: Therapeutic potential and clinical use. Future Med Chem 2009,1(9),1643-1670 10.4155/fmc.09.121 21425984 Buss J.; Torti F.; Torti S.; The role of iron chelation in cancer therapy. Curr Med Chem 2003,10(12),1021-1034 10.2174/0929867033457638 12678674 Dalamaga M.; Karampela I.; Mantzoros C.S.; Commentary: Could iron chelators prove to be useful as an adjunct to COVID-19 treatment regimens? Metabolism 2020,108,154260 10.1016/j.metabol.2020.154260 32418885 Williams A.; Meyer D.; Desferrioxamine as immunomodulatory agent during microorganism infection. Curr Pharm Des 2009,15(11),1261-1268 10.2174/138161209787846801 19355965 Liu W.; Zhang S.; Nekhai S.; Liu S.; Depriving iron supply to the virus represents a promising adjuvant therapeutic against viral survival. Curr Clin Microbiol Rep 2020,7(2),13-19 10.1007/s40588-020-00140-w 32318324 Saxena D.; Spino M.; Tricta F.; Connelly J.; Cracchiolo B.M.; Hanauske A.R.; D’Alliessi G.D.; Mathews M.B.; Karn J.; Holland B.; Park M.H.; Pe’ery T.; Palumbo P.E.; Hanauske-Abel H.M.; Drug-based lead discovery: the novel ablative antiretroviral profile of deferiprone in HIV-1-infected cells and in HIV-infected treatment-naive subjects of a double-blind, placebo-controlled, randomized exploratory trial. PLoS One 2016,11(5),e0154842 10.1371/journal.pone.0154842 27191165 Habib H.M.; Ibrahim S.; Zaim A.; Ibrahim W.H.; The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators. Biomed Pharmacother 2021,136,111228 10.1016/j.biopha.2021.111228 33454595 Khan N.; Chen X.; Geiger J.D.; Role of divalent cations in HIV-1 replication and pathogenicity. Viruses 2020,12(4),471 10.3390/v12040471 32326317 Farkas E.; Enyedy É.A.; Zékány L.; Deák G.; Interaction between iron(II) and hydroxamic acids: Oxidation of iron(II) to iron(III) by desferrioxamine B under anaerobic conditions. J Inorg Biochem 2001,83(2-3),107-114 10.1016/S0162-0134(00)00197-5 11237249 Shankaran P.; Madlenakova M.; Hajkova V.; Jilich D.; Svobodova I.; Horinek A.; Fujikura Y.; Melkova Z.; Effects of heme degradation products on reactivation of latent HIV-1. Acta Virol 2017,61(1),86-96 10.4149/av_2017_01_86 28161963 Muhoberac B.B.; What can cellular redox, iron, and reactive oxygen species suggest about the mechanisms and potential therapy of COVID-19? Front Cell Infect Microbiol 2020,10,569709 10.3389/fcimb.2020.569709 33381464 Abobaker A.; Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome? Eur J Clin Pharmacol 2020,76(11),1619-1620 10.1007/s00228-020-02942-9 32607779 Abobaker A.; Reply: Iron chelation may harm patients with COVID-19. Eur J Clin Pharmacol 2021,77(2),267-268 10.1007/s00228-020-02988-9 32870381 Zou D.M.; Rong D.D.; Zhao H.; Su L.; Sun W.L.; Improvement of chronic hepatitis B by iron chelation therapy in a patient with iron overload. Medicine 2017,96(52),e9566 10.1097/MD.0000000000009566 29384977 Masson P.L.; Heremans J.F.; Lactoferrin in milk from different species. Comp Biochem Physiol B 1971,39(1),119-IN13 10.1016/0305-0491(71)90258-6 4998849 Campione E.; Lanna C.; Cosio T.; Rosa L.; Conte M.P.; Iacovelli F.; Romeo A.; Falconi M.; Del Vecchio C.; Franchin E.; Lia M.S.; Minieri M.; Chiaramonte C.; Ciotti M.; Nuccetelli M.; Terrinoni A.; Iannuzzi I.; Coppeda L.; Magrini A.; Bernardini S.; Sabatini S.; Rosapepe F.; Bartoletti P.L.; Moricca N.; Di Lorenzo A.; Andreoni M.; Sarmati L.; Miani A.; Piscitelli P.; Valenti P.; Bianchi L.; Lactoferrin against SARS-CoV-2: In vitro and in silico evidence. Front Pharmacol 2021,12,666600 10.3389/fphar.2021.666600 34220505 Scott L.E.; Orvig C.; Medicinal inorganic chemistry approaches to passivation and removal of aberrant metal ions in disease. Chem Rev 2009,109(10),4885-4910 10.1021/cr9000176 19637926 Khodaverdian V.; Tapadar S.; MacDonald I.A.; Xu Y.; Ho P.Y.; Bridges A.; Rajpurohit P.; Sanghani B.A.; Fan Y.; Thangaraju M.; Hathaway N.A.; Oyelere A.K.; Deferiprone: Pan-selective histone lysine demethylase inhibition activity and structure- activity relationship study. Sci Rep 2019,9(1),4802 10.1038/s41598-019-39214-1 30886160 Suwanprinya L.; Morales N.P.; Sanvarinda P.; Dieng H.; Okabayashi T.; Morales Vargas R.E.; Dengue virus-induced reactive oxygen species production in rat microglial cells. Jpn J Infect Dis 2017,70(4),383-387 10.7883/yoken.JJID.2016.236 28003593 Joseph M.; Sreekanth A.; Suni V.; Kurup M.R.P.; Spectral characterization of iron(III) complexes of 2-benzoylpyridine N(4)-substituted thiosemicarbazones. Spectrochim Acta A Mol Biomol Spectrosc 2006,64(3),637-641 10.1016/j.saa.2005.07.067 16386946 Buesa J.; Grand challenge in viral disease investigation: An endless endeavor. Front Virol 2021,1,692105 10.3389/fviro.2021.692105 Allahverdipour H.; Global challenge of health communication: Infodemia in the coronavirus disease (COVID-19) pandemic. J Educ Community Health 2020,7(2),65-67 10.29252/jech.7.2.65 Chhabra R.; Saha A.; Chamani A.; Schneider N.; Shah R.; Nanjundan M.; Iron pathways and iron chelation approaches in viral, microbial, and fungal infections. Pharmaceuticals 2020,13(10),275 10.3390/ph13100275 32992923 Liu J.R.; Liu Y.; Yin F.Z.; Liu B.W.; Serum ferritin, an early marker of cardiovascular risk: a study in Chinese men of first-degree relatives with family history of type 2 diabetes. BMC Cardiovasc Disord 2019,19(1),82 10.1186/s12872-019-1068-5 30943893 Duchemin J.B.; Paradkar P.N.; Iron availability affects West Nile virus infection in its mosquito vector. Virol J 2017,14(1),103 10.1186/s12985-017-0770-0 28583206 Perricone C.; Bartoloni E.; Bursi R.; Cafaro G.; Guidelli G.M.; Shoenfeld Y.; Gerli R.; COVID-19 as part of the hyperferritinemic syndromes: The role of iron depletion therapy. Immunol Res 2020,68(4),213-224 10.1007/s12026-020-09145-5 32681497 van Asbeck B.S.; Georgiou N.A.; van der Bruggen T.; Oudshoorn M.; Nottet H.S.L.M.; Marx J.J.M.; Anti-HIV effect of iron chelators: Different mechanisms involved. J Clin Virol 2001,20(3),141-147 10.1016/S1386-6532(00)00122-0 11166663 Debebe Z.; Ammosova T.; Jerebtsova M.; Kurantsin-Mills J.; Niu X.; Charles S.; Richardson D.R.; Ray P.E.; Gordeuk V.R.; Nekhai S.; Iron chelators ICL670 and 311 inhibit HIV-1 transcription. Virology 2007,367(2),324-333 10.1016/j.virol.2007.06.011 17631934 Ricchi P.; Cinque P.; Lanza Galeota A.; Di Matola T.; Ammirabile M.; Prossomariti L.; Hepatitis B virus reactivation during combined therapy with deferiprone and desferioxamine in a hepatitis B surface antigen thalassemic carrier. Int J Hematol 2009,89(2),135-138 10.1007/s12185-008-0229-6 19107332 Flora S.J.S.; Pachauri V.; Chelation in metal intoxication. Int J Environ Res Public Health 2010,7(7),2745-2788 10.3390/ijerph7072745 20717537 Mancinelli R.; Rosa L.; Cutone A.; Lepanto M.S.; Franchitto A.; Onori P.; Gaudio E.; Valenti P.; Viral hepatitis and iron dysregulation: Molecular pathways and the role of lactoferrin. Molecules 2020,25(8),1997 10.3390/molecules25081997 32344579 Singh A.; Ahmad N.; Varadarajan A.; Vikram N.; Singh T.P.; Sharma S.; Sharma P.; Lactoferrin, a potential iron-chelator as an adjunct treatment for mucormycosis – A comprehensive review. Int J Biol Macromol 2021,187,988-998 10.1016/j.ijbiomac.2021.07.156 34324905 Arandi N.; Haghpanah S.; Safaei S.; Zahedi Z.; Ashrafi A.; Eatemadfar P.; Zarei T.; Radwan A.H.; Taher A.T.; Karimi M.; Combination therapy – deferasirox and deferoxamine – in thalassemia major patients in emerging countries with limited resources. Transfus Med 2015,25(1),8-12 10.1111/tme.12188 25801075 Voskaridou E.; Komninaka V.; Karavas A.; Terpos E.; Akianidis V.; Christoulas D.; Combination therapy of deferasirox and deferoxamine shows significant improvements in markers of iron overload in a patient with β-thalassemia major and severe iron burden. Transfusion 2014,54(3),646-649 10.1111/trf.12335 23834310 Sane A.; Manzi S.; Perfect J.; Herzberg A.J.; Moore J.O.; Deferoxamine treatment as a risk factor for zygomycete infection. J Infect Dis 1989,159(1),151-152 10.1093/infdis/159.1.151 2909637 Kontoghiorghes G.J.; New concepts of iron and aluminium chelation therapy with oral L1 (deferiprone) and other chelators. A review. Analyst 1995,120(3),845-851 10.1039/an9952000845 7741239 Addis A.; Loebstein R.; Koren G.; Einarson T.R.; Meta-analytic review of the clinical effectiveness of oral deferiprone (L 1 ). Eur J Clin Pharmacol 1999,55(1),1-6 10.1007/s002280050584 10206077 Chen X.; Yu C.; Kang R.; Tang D.; Iron metabolism in ferroptosis. Front Cell Dev Biol 2020,8,590226 10.3389/fcell.2020.590226 33117818 Dixon SJ; Lemberg KM; Lamprecht MR; Skouta R; Zaitsev EM; Gleason CE; Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 2012,149(5),1060-1072 Yao X.; Zhang Y.; Fan B-Y.; Pang Y-L.; Shen W-Y.; Wang X.; Zhao C-X.; Li W-X.; Liu C.; Kong X-H.; Ning G-Z.; Feng S-Q.; Neuroprotective effect of deferoxamine on erastininduced ferroptosis in primary cortical neurons. Neural Regen Res 2020,15(8),1539-1545 10.4103/1673-5374.274344 31997820 Grignano E.; Birsen R.; Chapuis N.; Bouscary D.; From iron chelation to overload as a therapeutic strategy to induce ferroptosis in leukemic cells. Front Oncol 2020,10,586530 10.3389/fonc.2020.586530 33042852

Rights & Permissions Print Cite

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/0109298673259596231211113211	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X

Current Medicinal Chemistry

Therapeutic Potential of Iron Chelators in Viral Diseases: A Systematic Review

Abstract Play Pause

Related Journals

Related Books

Abstract