{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T11:06:40Z","timestamp":1775473600366,"version":"3.50.1"},"reference-count":200,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2017\/26\/A\/ST5\/00363"],"award-info":[{"award-number":["UMO-2017\/26\/A\/ST5\/00363"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2017\/26\/A\/ST5\/00364"],"award-info":[{"award-number":["UMO-2017\/26\/A\/ST5\/00364"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Zn(II) is an inhibitor of SARS-CoV-2\u2032s RNA-dependent RNA polymerase, and chloroquine and hydroxychloroquine are Zn(II) ionophores\u2013this statement gives a curious mind a lot to think about. We show results of the first clinical trials on chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19, as well as earlier reports on the anticoronaviral properties of these two compounds and of Zn(II) itself. Other FDA-approved Zn(II) ionophores are given a decent amount of attention and are thought of as possible COVID-19 therapeutics.<\/jats:p>","DOI":"10.3390\/ph13090228","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T08:53:43Z","timestamp":1598950423000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Zinc(II)\u2014The Overlooked \u00c9minence Grise of Chloroquine\u2019s Fight against COVID-19?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-9599","authenticated-orcid":false,"given":"Aleksandra","family":"Hecel","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-8914","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Ostrowska","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamila","family":"Stokowa-So\u0142tys","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"W\u0105t\u0142y","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4699-7665","authenticated-orcid":false,"given":"Dorota","family":"Dudek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Miller","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u0142awomir","family":"Potocki","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1064-1237","authenticated-orcid":false,"given":"Agnieszka","family":"Matera-Witkiewicz","sequence":"additional","affiliation":[{"name":"Screening Laboratory of Biological Activity Tests and Collection of Biological Material, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Dominguez-Martin","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Pharmacy, University of Granada, E-18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henryk","family":"Koz\u0142owski","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"},{"name":"Department of Physiotherapy, Opole Medical School, Katowicka 68, 40-060 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0425-1128","authenticated-orcid":false,"given":"Magdalena","family":"Rowi\u0144ska-\u017byrek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Te Velthuis, A.J.W., van den Worm, S.H.E., Sims, A.C., Baric, R.S., Snijder, E.J., and van Hemert, M.J. (2010). Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001176"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xue, J., Moyer, A., Peng, B., Wu, J., Hannafon, B.N., and Ding, W.-Q. (2014). Chloroquine Is a Zinc Ionophore. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109180"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"72","DOI":"10.5582\/bst.2020.01047","article-title":"Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies","volume":"14","author":"Gao","year":"2020","journal-title":"Biosci. Trends"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105949","DOI":"10.1016\/j.ijantimicag.2020.105949","article-title":"Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial","volume":"56","author":"Gautret","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yu, B., Li, C., Chen, P., Zhou, N., Wang, L., Li, J., Jiang, H., and Wang, D.-W. (2020). Erratum to: Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19. Sci. China Life Sci.","DOI":"10.1007\/s11427-020-1751-3"},{"key":"ref_6","first-page":"m1844","article-title":"Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: Observational comparative study using routine care data","volume":"369","author":"Tran","year":"2020","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mehra, M.R., Desai, S.S., Ruschitzka, F., and Patel, A.N. (2020). RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis. Lancet.","DOI":"10.1016\/S0140-6736(20)31180-6"},{"key":"ref_8","unstructured":"World Health Organization (2020, July 07). WHO Director-General\u2019s Opening Remarks at the Media Briefing on COVID-19\u201425 May 2020. Available online: https:\/\/www.who.int\/dg\/speeches\/detail\/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---25-may-2020."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"The Lancet Editors (2020). Expression of concern: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis. Lancet, 395, e102.","DOI":"10.1016\/S0140-6736(20)31290-3"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1016\/S0140-6736(20)31324-6","article-title":"Retraction\u2014Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis","volume":"395","author":"Mehra","year":"2020","journal-title":"Lancet"},{"key":"ref_11","first-page":"e102","article-title":"Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19","volume":"382","author":"Mehra","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Scholz, M., and Derwand, R. (2020). Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine\/Hydroxychloroquine to Win Todays Battle Against COVID-19?. Preprints, 109815.","DOI":"10.20944\/preprints202004.0124.v1"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Scholz, M., Derwand, R., and Zelenko, V. (2020). COVID-19 Outpatients\u2013Early Risk\u2013Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study. Preprints, 2020070025.","DOI":"10.20944\/preprints202007.0025.v1"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Carlucci, P., Ahuja, T., Petrilli, C.M., Rajagopalan, H., Jones, S., and Rahimian, J. (2020). Hydroxychloroquine and azithromycin plus zinc vs. hydroxychloroquine and azithromycin alone: Outcomes in hospitalized COVID-19 patients. medRixv.","DOI":"10.1101\/2020.05.02.20080036"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8181","DOI":"10.1128\/JVI.77.15.8181-8186.2003","article-title":"Host Factors in Positive-Strand RNA Virus Genome Replication","volume":"77","author":"Ahlquist","year":"2003","journal-title":"JVI"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.2000.0421","article-title":"Synthesis of Subgenomic RNAs by Positive-Strand RNA Viruses","volume":"273","author":"Miller","year":"2000","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10674","DOI":"10.1074\/jbc.M111.325530","article-title":"Assembly, purification, and pre-steady-state kinetic analysis of active RNA-dependent RNA polymerase elongation complex","volume":"287","author":"Jin","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrmicro2147","article-title":"Coronaviruses post-SARS: Update on replication and pathogenesis","volume":"7","author":"Perlman","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nrmicro775","article-title":"SARS--beginning to understand a new virus","volume":"1","author":"Stadler","year":"2003","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virusres.2006.01.017","article-title":"Nidovirales: Evolving the largest RNA virus genome","volume":"117","author":"Gorbalenya","year":"2006","journal-title":"Virus Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1038\/s41467-019-10280-3","article-title":"Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors","volume":"10","author":"Kirchdoerfer","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1126\/science.abb7498","article-title":"Structure of the RNA-dependent RNA polymerase from COVID-19 virus","volume":"368","author":"Gao","year":"2020","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7117","DOI":"10.1093\/nar\/gkg916","article-title":"Molecular model of SARS coronavirus polymerase: Implications for biochemical functions and drug design","volume":"31","author":"Xu","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nrmicro975","article-title":"Antivirals and antiviral strategies","volume":"2","author":"Clercq","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0166-3542(02)00109-2","article-title":"Effect of antioxidants on apoptosis induced by influenza virus infection: Inhibition of viral gene replication and transcription with pyrrolidine dithiocarbamate","volume":"56","author":"Uchide","year":"2002","journal-title":"Antivir. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1128\/AAC.48.3.783-790.2004","article-title":"Effect of zinc salts on respiratory syncytial virus replication","volume":"48","author":"Suara","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6004","DOI":"10.1128\/JVI.76.12.6004-6015.2002","article-title":"Antiviral Effects of Pyrrolidine Dithiocarbamate on Human Rhinoviruses","volume":"76","author":"Gaudernak","year":"2002","journal-title":"JVI"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8014","DOI":"10.1128\/JVI.79.13.8014-8023.2005","article-title":"Pyrrolidine dithiocarbamate reduces coxsackievirus B3 replication through inhibition of the ubiquitin-proteasome pathway","volume":"79","author":"Si","year":"2005","journal-title":"JVI"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/248588a0","article-title":"Zinc ions inhibit replication of rhinoviruses","volume":"248","author":"Korant","year":"1974","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1128\/AAC.13.5.731","article-title":"Effect of Zinc and Other Chemical Agents on Foot-and-Mouth Disease Virus Replication","volume":"13","author":"Polatnick","year":"1978","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1099\/vir.0.82634-0","article-title":"PDTC inhibits picornavirus polyprotein processing and RNA replication by transporting zinc ions into cells","volume":"88","author":"Lanke","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1128\/JVI.01543-08","article-title":"Antiviral Activity of the Zinc Ionophores Pyrithione and Hinokitiol against Picornavirus Infections","volume":"83","author":"Krenn","year":"2009","journal-title":"JVI"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0166-3542(99)00040-6","article-title":"Inhibition of HIV-1 infection by zinc group metal compounds","volume":"43","author":"Haraguchi","year":"1999","journal-title":"Antivir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1128\/AAC.19.2.213","article-title":"Inhibition of vaccinia virus maturation by zinc chloride","volume":"19","author":"Katz","year":"1981","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","first-page":"2989","article-title":"The mechanism of the antiherpetic activity of zinc sulphate","volume":"71 Pt 12","author":"Schrader","year":"1990","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1128\/jvi.18.1.298-306.1976","article-title":"Inhibition by zinc of rhinovirus protein cleavage: Interaction of zinc with capsid polypeptides","volume":"18","author":"Korant","year":"1976","journal-title":"JVI"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0306-9877(96)90259-5","article-title":"How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action","volume":"46","author":"Novick","year":"1996","journal-title":"Med. Hypotheses"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1099\/0022-1317-23-1-59","article-title":"Inhibition of the particle-associated RNA-dependent RNA polymerase activity of influenza viruses by chelating agents","volume":"23","author":"Oxford","year":"1974","journal-title":"J. Gen. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1128\/JVI.73.2.1649-1654.1999","article-title":"Characterization of Soluble Hepatitis C Virus RNA-Dependent RNA Polymerase Expressed in Escherichia coli","volume":"73","author":"Ferrari","year":"1999","journal-title":"JVI"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0166-3542(02)00101-8","article-title":"Biochemical characterization of rhinovirus RNA-dependent RNA polymerase","volume":"56","author":"Hung","year":"2002","journal-title":"Antivir. Res."},{"key":"ref_41","unstructured":"(2002). The PyMOL Molecular Graphics System, Schr\u00f6dinger, LLC. Version 1.8."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gao, Y., Yan, L., Huang, Y., Liu, F., Cao, L., Wang, T., Wang, Q., Lou, Z., and Rao, Z. (2020, April 15). SARS-CoV-2 RNA-Dependent RNA Polymerase in Complex with Cofactors in Reduced Condition. Available online: https:\/\/www.rcsb.org\/structure\/7btf.","DOI":"10.2210\/pdb7btf\/pdb"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41421-020-0156-0","article-title":"Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro","volume":"6","author":"Liu","year":"2020","journal-title":"Cell Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0002-9343(83)91265-2","article-title":"Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate","volume":"75","author":"McChesney","year":"1983","journal-title":"Am. J. Med."},{"key":"ref_45","unstructured":"(2020, April 23). COVID-19: Reminder of Risk of Serious Side Effects with Chloroquine and Hydroxychloroquine, Available online: http:\/\/urpl.gov.pl\/sites\/default\/files\/CQ-HCQ%20-%2004-2020%20-%20public%20health%20communication_0.pdf."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10787-015-0239-y","article-title":"Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases","volume":"23","author":"Rainsford","year":"2015","journal-title":"Inflammopharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00436-012-2886-x","article-title":"From methylene blue to chloroquine: A brief review of the development of an antimalarial therapy","volume":"111","author":"Krafts","year":"2012","journal-title":"Parasitol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R135","DOI":"10.1186\/ar3868","article-title":"Hydroxychloroquine improves insulin sensitivity in obese non-diabetic individuals","volume":"14","author":"Mercer","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1001\/jama.2011.878","article-title":"Association between disease-modifying antirheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis","volume":"305","author":"Solomon","year":"2011","journal-title":"JAMA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.imlet.2013.07.004","article-title":"Chloroquine: Modes of action of an undervalued drug","volume":"153","author":"Lopes","year":"2013","journal-title":"Immunol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/S1473-3099(03)00806-5","article-title":"Effects of chloroquine on viral infections: An old drug against today\u2019s diseases","volume":"3","author":"Savarino","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"D708","DOI":"10.1093\/nar\/gkx932","article-title":"Virus taxonomy: The database of the International Committee on Taxonomy of Viruses (ICTV)","volume":"46","author":"Lefkowitz","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.bbrc.2004.08.085","article-title":"In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine","volume":"323","author":"Keyaerts","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrd.2015.37","article-title":"Coronaviruses-drug discovery and therapeutic options","volume":"15","author":"Zumla","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1743-422X-2-69","article-title":"Chloroquine is a potent inhibitor of SARS coronavirus infection and spread","volume":"2","author":"Vincent","year":"2005","journal-title":"Virol. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.7150\/ijbs.45498","article-title":"Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19","volume":"16","author":"Yang","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.virol.2017.12.015","article-title":"Physiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells","volume":"517","author":"Millet","year":"2018","journal-title":"Virology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11876","DOI":"10.1073\/pnas.0505577102","article-title":"Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry","volume":"102","author":"Simmons","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41422-020-0282-0","article-title":"Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro","volume":"30","author":"Wang","year":"2020","journal-title":"Cell Res."},{"key":"ref_60","unstructured":"(2020, April 15). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1128\/AAC.03011-14","article-title":"Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture","volume":"58","author":"Jochmans","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_62","unstructured":"Goldman, L., and La Cecil, R.F. (2011). Goldman\u2019s Cecil Medicine, Saunders. [24th ed.]."},{"key":"ref_63","unstructured":"Pelczar, M.J. (2010). Microbiology (An Application Based Approach), Tata McGraw Hill Education Private Limited. [1st ed.]."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1128\/AAC.01509-08","article-title":"Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice","volume":"53","author":"Keyaerts","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.antiviral.2007.10.011","article-title":"Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK","volume":"77","author":"Kono","year":"2008","journal-title":"Antivir. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.virusres.2018.05.028","article-title":"Role of MAPK\/MNK1 signaling in virus replication","volume":"253","author":"Kumar","year":"2018","journal-title":"Virus Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cvsm.2004.10.011","article-title":"Feline infectious peritonitis","volume":"35","author":"Hartmann","year":"2005","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.antiviral.2013.04.016","article-title":"Effect of chloroquine on feline infectious peritonitis virus infection in vitro and in vivo","volume":"99","author":"Takano","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_69","unstructured":"ClinicalTrials.gov (2020, April 15). A Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection (HELPCOVID-19), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04335084."},{"key":"ref_70","unstructured":"ClinicalTrials.gov (2020, April 15). Proflaxis Using Hydroxychloroquine Plus Vitamins-Zinc During COVID-19 Pandemia, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04326725."},{"key":"ref_71","unstructured":"ClinicalTrials.gov (2020, April 15). A Study of Quintuple Therapy to Treat COVID-19 Infection (HAZDpaC), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04334512."},{"key":"ref_72","unstructured":"ClinicalTrials.gov (2020, April 15). Anti-inflammatory\/Antioxidant Oral Nutrition Supplementation in COVID-19 (ONSCOVID19), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04323228."},{"key":"ref_73","unstructured":"ClinicalTrials.gov (2020, April 15). Coronavirus 2019 (COVID-19)-Using Ascorbic Acid and Zinc Supplementation (COVIDAtoZ), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04342728."},{"key":"ref_74","unstructured":"ClinicalTrials.gov (2020, July 07). Hydroxychloroquine and Zinc with Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04370782."},{"key":"ref_75","unstructured":"ClinicalTrials.gov (2020, July 07). A Study of Hydroxychloroquine and Zinc in the Prevention of COVID-19 Infection in Military Healthcare Workers (COVID-Milit), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04377646."},{"key":"ref_76","unstructured":"ClinicalTrials.gov (2020, July 07). Impact of Zinc and Vitamin D3 Supplementation on the Survival of Aged Patients Infected With COVID-19 (ZnD3-CoVici), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04351490."},{"key":"ref_77","unstructured":"ClinicalTrials.gov (2020, August 28). Early Intervention in COVID-19: Favipiravir Verses Standard Care (PIONEER), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04373733."},{"key":"ref_78","unstructured":"ClinicalTrials.gov (2020, July 07). Zinc with Chloroquine\/Hydroxychloroquine in Treatment of COVID-19, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04447534."},{"key":"ref_79","unstructured":"ClinicalTrials.gov (2020, July 07). International ALLIANCE Study of Therapies to Prevent Progression of COVID-19, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04395768."},{"key":"ref_80","unstructured":"ClinicalTrials.gov (2020, July 07). COVID-19 Prophylaxis with Hydroxychloroquine Associated with Zinc for High-Risk Healthcare Workers, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04384458."},{"key":"ref_81","unstructured":"ClinicalTrials.gov (2020, July 07). A Preventive Treatment for Migrant Workers at High-risk of Covid-19, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04446104."},{"key":"ref_82","unstructured":"ClinicalTrials.gov (2020, July 07). New Antiviral Drugs for Treatment of COVID-19, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04392427."},{"key":"ref_83","unstructured":"ClinicalTrials.gov (2020, July 07). Covid-19 and Diabetes in West of Algeria (COVIDIAB-13), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04412746."},{"key":"ref_84","unstructured":"ClinicalTrials.gov (2020, July 30). The Study of Quadruple Therapy Zinc, Quercetin, Bromelain and Vitamin C on the Clinical Outcomes of Patients Infected with COVID-19, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04468139."},{"key":"ref_85","unstructured":"ClinicalTrials.gov (2020, July 30). Efficacy of Subcutaneous Ivermectin with or without Zinc and Nigella Sativa in COVID-19 Patients (SINZ-COVID-PK), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04472585."},{"key":"ref_86","unstructured":"ClinicalTrials.gov (2020, July 30). Clearing the Fog: Is Hydroxychloroquine Effective in Reducing COVID-19 Progression (COVID-19), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04491994."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Milewska, A., Chi, Y., Szczepanski, A., Barreto-Duran, E., Liu, K., Liu, D., Guo, X., Ge, Y., Li, J., and Cui, L. (2020). HTCC as a highly effective polymeric inhibitor of SARS-CoV-2 and MERS-CoV. bioRxiv.","DOI":"10.1101\/2020.03.29.014183"},{"key":"ref_89","unstructured":"Rut, W., Groborz, K., Zhang, L., Sun, X., Zmudzinski, M., Hilgenfeld, R., and Drag, M. (2020). Substrate specificity profiling of SARS-CoV-2 M pro protease provides basis for anti-COVID-19 drug design. bioRxiv."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved \u03b1-ketoamide inhibitors","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10349","DOI":"10.1021\/bi0504761","article-title":"Papain-like protease 2 (PLP2) from severe acute respiratory syndrome coronavirus (SARS-CoV): Expression, purification, characterization, and inhibition","volume":"44","author":"Han","year":"2005","journal-title":"Biochemistry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4933","DOI":"10.1038\/sj.emboj.7601368","article-title":"A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus","volume":"25","author":"Imbert","year":"2006","journal-title":"EMBO J."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.2174\/092986706777584988","article-title":"Antiviral drug discovery against SARS-CoV","volume":"13","author":"Wu","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Adedeji, A.O., Marchand, B., te Velthuis, A.J.W., Snijder, E.J., Weiss, S., Eoff, R.L., Singh, K., and Sarafianos, S.G. (2012). Mechanism of nucleic acid unwinding by SARS-CoV helicase. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036521"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S1386-6532(00)00140-2","article-title":"The potential place of chloroquine in the treatment of HIV-1-infected patients","volume":"20","author":"Boelaert","year":"2001","journal-title":"J. Clin. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S1386-6532(00)00139-6","article-title":"The anti-HIV-1 activity of chloroquine","volume":"20","author":"Savarino","year":"2001","journal-title":"J. Clin. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4690-4-6","article-title":"Effect of chloroquine on reducing HIV-1 replication in vitro and the DC-SIGN mediated transfer of virus to CD4 + T-lymphocytes","volume":"4","author":"Naarding","year":"2007","journal-title":"Retrovirology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/00126334-200403010-00002","article-title":"Anti-HIV Effects of Chloroquine: Inhibition of viral particle glycosylation and synergism with protease inhibitors","volume":"35","author":"Savarino","year":"2004","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.2174\/1381612043383791","article-title":"Chloroquine and Hydroxychloroquine as Inhibitors of Human Immunodeficiency Virus (HIV-1) Activity","volume":"10","author":"Romanelli","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_100","first-page":"2221","article-title":"Anti-HIV effects of chloroquine: Mechanisms of inhibition and spectrum of activity","volume":"15","author":"Savarino","year":"2001","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0165-2478(98)00096-0","article-title":"Chloroquine inhibits HIV-1 replication in human peripheral blood lymphocytes","volume":"64","author":"Pardridge","year":"1998","journal-title":"Immunol. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1159\/000024948","article-title":"Examination of potential inhibitors of hepatitis A virus uncoating","volume":"41","author":"Bishop","year":"1998","journal-title":"Intervirology"},{"key":"ref_103","first-page":"149","article-title":"Treatment of chronic active hepatitis B (CAH B) with chloroquine: A preliminary report","volume":"15","author":"Kouroumalis","year":"1986","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00535-009-0132-9","article-title":"Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy","volume":"45","author":"Mizui","year":"2010","journal-title":"J. Gastroenterol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/jgh3.12258","article-title":"Efficacy and safety of chloroquine plus prednisone for the treatment of autoimmune hepatitis in a randomized trial","volume":"4","author":"Terrabuio","year":"2020","journal-title":"JGH Open"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7008","DOI":"10.1128\/jvi.65.12.7008-7011.1991","article-title":"Chloroquine induces empty capsid formation during poliovirus eclipse","volume":"65","author":"Kronenberger","year":"1991","journal-title":"JVI"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1743-422X-3-39","article-title":"In vitro inhibition of human influenza a virus replication by chloroquine","volume":"3","author":"Ooi","year":"2006","journal-title":"Virol. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1750-2659.2007.00027.x","article-title":"Chloroquine is effective against influenza A virus in vitro but not in vivo","volume":"1","author":"Vigerust","year":"2007","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1099\/0022-1317-64-5-1149","article-title":"Mechanism of Uncoating of Influenza B Virus in MDCK Cells: Action of Chloroquine","volume":"64","author":"Shibata","year":"1983","journal-title":"J. Gen. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/cr.2012.165","article-title":"Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model","volume":"23","author":"Yan","year":"2013","journal-title":"Cell Res."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Delvecchio, R., Higa, L.M., Pezzuto, P., Valad\u00e3o, A.L., Garcez, P.P., Monteiro, F.L., Loiola, E.C., Dias, A.A., Silva, F.J.M., and Aliota, M.T. (2016). Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models. Viruses, 8.","DOI":"10.1101\/051268"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ebiom.2017.09.034","article-title":"Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice","volume":"24","author":"Li","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"104547","DOI":"10.1016\/j.antiviral.2019.104547","article-title":"Chloroquine inhibits endosomal viral RNA release and autophagy-dependent viral replication and effectively prevents maternal to fetal transmission of Zika virus","volume":"169","author":"Zhang","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1099\/jgv.0.000309","article-title":"Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model","volume":"96","author":"Dowall","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.antiviral.2015.03.005","article-title":"Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules","volume":"118","author":"Ferraris","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/BF01310010","article-title":"Ammonium chloride and chloroquine inhibit rabies virus infection in neuroblastoma cells. Brief report","volume":"81","author":"Tsiang","year":"1984","journal-title":"Arch. Virol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/jmv.21663","article-title":"Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against Chikungunya virus in vero cells","volume":"82","author":"Khan","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1002\/jmv.22019","article-title":"Chikungunya disease and chloroquine treatment","volume":"83","author":"Delogu","year":"2011","journal-title":"J. Med. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/282734","article-title":"Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6\/36 Cells","volume":"2013","author":"Farias","year":"2013","journal-title":"Sci. World J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/1348-0421.12154","article-title":"Chloroquine interferes with dengue-2 virus replication in U937 cells","volume":"58","author":"Farias","year":"2014","journal-title":"Microbiol. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1089\/vim.2014.0090","article-title":"Antiviral Activity of Chloroquine Against Dengue Virus Type 2 Replication in Aotus Monkeys","volume":"28","author":"Farias","year":"2015","journal-title":"Viral Immunol."},{"key":"ref_122","first-page":"765","article-title":"Combined chloroquine and ribavirin treatment does not prevent death in a hamster model of Nipah and Hendra virus infection","volume":"91","author":"Freiberg","year":"2010","journal-title":"Arch. Virol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/0042-6822(84)90356-8","article-title":"Inhibition of multiplication of herpes simplex virus type 1 by ammonium chloride and chloroquine","volume":"138","author":"Koyama","year":"1984","journal-title":"Virology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/0149-2918(95)80039-5","article-title":"Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1","volume":"17","author":"Sperber","year":"1995","journal-title":"Clin. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0149-2918(97)80045-8","article-title":"Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1","volume":"19","author":"Sperber","year":"1997","journal-title":"Clin. Ther."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1089\/aid.1993.9.91","article-title":"Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes","volume":"9","author":"Sperber","year":"1993","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1073\/pnas.90.6.2399","article-title":"Inhibitors of human immunodeficiency virus integrase","volume":"90","author":"Fesen","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/bbrc.1996.1302","article-title":"Inhibition of HIV-1 Tat-mediated transactivation by quinacrine and chloroquine","volume":"226","author":"Jiang","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_129","first-page":"91","article-title":"Effects of chloroquine on iron metabolism in a lymphocytic cell line","volume":"16","author":"Morra","year":"2000","journal-title":"J. Clin. Virol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1089\/aid.1990.6.481","article-title":"Inhibition of human immunodeficiency virus infectivity by chloroquine","volume":"6","author":"Tsai","year":"1990","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Tricou, V., Minh, N.N., Van, T.P., Lee, S.J., Farrar, J., Wills, B., Tran, H.T., and Simmons, C.P. (2010). A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adults. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000785"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1590\/S0074-02762013000500010","article-title":"Chloroquine use improves dengue-related symptoms","volume":"108","author":"Borges","year":"2013","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Madrid, P.B., Chopra, S., Manger, I.D., Gilfillan, L., Keepers, T.R., Shurtleff, A.C., Green, C.E., Iyer, L.V., Dilks, H.H., and Davey, R.A. (2013). A systematic screen of FDA-approved drugs for inhibitors of biological threat agents. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060579"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.vetmic.2017.01.033","article-title":"Pyrithione inhibits porcine reproductive and respiratory syndrome virus replication through interfering with NF-\u03baB and heparanase","volume":"201","author":"Guo","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.antiviral.2013.07.001","article-title":"Zinc ionophores pyrithione inhibits herpes simplex virus replication through interfering with proteasome function and NF-\u03baB activation","volume":"100","author":"Qiu","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1016\/j.fct.2007.05.015","article-title":"A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic\/carcinogenic properties","volume":"45","author":"Harwood","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.3390\/molecules16032032","article-title":"Antioxidant therapy as a potential approach to severe influenza-associated complications","volume":"16","author":"Uchide","year":"2011","journal-title":"Molecules"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Wu, W., Li, R., Li, X., He, J., Jiang, S., Liu, S., and Yang, J. (2016). Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses, 8.","DOI":"10.3390\/v8010006"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s12250-015-3584-5","article-title":"Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines","volume":"30","author":"Cheng","year":"2015","journal-title":"Virol. Sin."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/srep31777","article-title":"Effect of Quercetin on Hepatitis C Virus Life Cycle: From Viral to Host Targets","volume":"6","author":"Rojas","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e81","DOI":"10.1111\/j.1365-2893.2011.01507.x","article-title":"Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity","volume":"19","author":"Bachmetov","year":"2012","journal-title":"J. Viral. Hepat."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.1128\/AAC.00307-16","article-title":"Prophylactic Efficacy of Quercetin 3-\u03b2- O -d-Glucoside against Ebola Virus Infection","volume":"60","author":"Qiu","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.apjtm.2015.12.002","article-title":"Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection","volume":"9","author":"Chiow","year":"2016","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"16785","DOI":"10.3390\/ijms131216785","article-title":"Antiviral Activity of Baicalein and Quercetin against the Japanese Encephalitis Virus","volume":"13","author":"Johari","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s12250-017-4057-9","article-title":"Antiviral activity of quercetin-3-\u03b2-O-D-glucoside against Zika virus infection","volume":"32","author":"Wong","year":"2017","journal-title":"Virol. Sin."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0005-2736(03)00158-5","article-title":"Early steps of the conformational change of influenza virus hemagglutinin to a fusion active state","volume":"1614","author":"Huang","year":"2003","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1021\/jm0508888","article-title":"Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors","volume":"49","author":"Gaspari","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.bmcl.2005.01.083","article-title":"Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains","volume":"15","author":"Cao","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s10495-015-1114-4","article-title":"A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression of the E6 oncogene of human papillomavirus 18 in HeLa cells","volume":"20","author":"Li","year":"2015","journal-title":"Apoptosis"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/0140-6736(90)90802-C","article-title":"Inhibition of HIV progression by dithiocarb","volume":"335","author":"Reisinger","year":"1990","journal-title":"Lancet"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.7164\/antibiotics.37.1501","article-title":"The structure and absolute stereochemistry of zincophorin (antibiotic M144255): A monobasic carboxylic acid ionophore having a remarkable specificity for divalent cations","volume":"37","author":"Brooks","year":"1984","journal-title":"J. Antibiot."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"836","DOI":"10.7164\/antibiotics.37.836","article-title":"Griseochelin, a novel carboxylic acid antibiotic from Streptomyces griseus","volume":"37","author":"Schade","year":"1984","journal-title":"J. Antibiot."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1039\/c39840000599","article-title":"The constitution of griseochelin","volume":"1010","author":"Radics","year":"1984","journal-title":"J. Chem. Soc. Chem. Commun."},{"key":"ref_154","unstructured":"Gr\u00e4fe, U., Tonew, E., Schade, W., Reinhardt, G., and Hartl, A. (1986). Ger. (East). Patent DD 231 793."},{"key":"ref_155","first-page":"717","article-title":"Griseochelinmethylester, ein neues Polyether-Derivat mit antiviraler Wirksamkeit","volume":"43","author":"Tonew","year":"1988","journal-title":"Pharmazie"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.bcp.2005.01.001","article-title":"Anticancer metal compounds in NCI\u2019s tumor-screening database: Putative mode of action","volume":"69","author":"Huang","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.2174\/092986712800609698","article-title":"Metal transport and homeostasis within the human body: Toxicity associated with transport abnormalities","volume":"19","author":"Potocki","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5318","DOI":"10.1158\/0008-5472.CAN-08-0601","article-title":"Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores","volume":"68","author":"Magda","year":"2008","journal-title":"Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1002\/iub.253","article-title":"Metal ionophores: An emerging class of anticancer drugs","volume":"61","author":"Ding","year":"2009","journal-title":"IUBMB Life"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.2174\/0929867033457557","article-title":"Iron chelators as anti-neoplastic agents: Current developments and promise of the PIH class of chelators","volume":"10","author":"Lovejoy","year":"2003","journal-title":"Curr. Med. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/03630260701727119","article-title":"Chelators Controlling Metal Metabolism and Toxicity Pathways: Applications in Cancer Prevention, Diagnosis and Treatment","volume":"32","author":"Kontoghiorghes","year":"2008","journal-title":"Hemoglobin"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Gaur, K., V\u00e1zquez-Salgado, A., Duran-Camacho, G., Dominguez-Martinez, I., Benjam\u00edn-Rivera, J., Fern\u00e1ndez-Vega, L., Carmona Sarabia, L., Cruz Garc\u00eda, A., P\u00e9rez-Deliz, F., and M\u00e9ndez Rom\u00e1n, J. (2018). Iron and Copper Intracellular Chelation as an Anticancer Drug Strategy. Inorganics, 6.","DOI":"10.3390\/inorganics6040126"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1006\/bbrc.1999.0814","article-title":"Pyrithione, a zinc ionophore, inhibits NF-kappaB activation","volume":"259","author":"Kim","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Knight, D.W., and Hartung, J. (2001). 1-Hydroxypyridine-2(1H)-thione. Encyclopedia of Reagents for Organic Synthesis, John Wiley & Sons, Ltd.","DOI":"10.1002\/047084289X.rh067"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1196\/annals.1299.056","article-title":"Effect of zinc on prostatic tumorigenicity in nude mice","volume":"1010","author":"Feng","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1158\/0008-5472.CAN-04-3577","article-title":"Anticancer activity of the antibiotic clioquinol","volume":"65","author":"Ding","year":"2005","journal-title":"Cancer Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1001\/archneur.60.12.1685","article-title":"Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: A pilot phase 2 clinical trial","volume":"60","author":"Ritchie","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"11623","DOI":"10.1016\/S0021-9258(19)86530-4","article-title":"Reaction of copper-zinc superoxide dismutase with diethyldithiocarbamate","volume":"254","author":"Misra","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1084\/jem.175.5.1181","article-title":"Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells","volume":"175","author":"Schreck","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1128\/MCB.17.10.5699","article-title":"Regulation of p53 by metal ions and by antioxidants: Dithiocarbamate down-regulates p53 DNA-binding activity by increasing the intracellular level of copper","volume":"17","author":"Verhaegh","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"18898","DOI":"10.1074\/jbc.273.30.18898","article-title":"Pyrrolidine dithiocarbamate prevents p53 activation and promotes p53 cysteine residue oxidation","volume":"273","author":"Wu","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"26202","DOI":"10.1074\/jbc.270.44.26202","article-title":"Dithiocarbamates induce apoptosis in thymocytes by raising the intracellular level of redox-active copper","volume":"270","author":"Nobel","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1046\/j.1471-4159.1999.721586.x","article-title":"Pyrrolidine Dithiocarbamate Induces Bovine Cerebral Endothelial Cell Death by Increasing the Intracellular Zinc Level","volume":"72","author":"Kim","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_174","unstructured":"Robinson, N.E., and Sprayberry, K.A. (2015). Common Toxins in Equine Practice. Equine Medicine, Elsevier. [7th ed.]."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1039\/C8RA07641C","article-title":"Synthetic ionophores as non-resistant antibiotic adjuvants","volume":"9","author":"Patel","year":"2019","journal-title":"RSC Adv."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/162513","article-title":"Structures and Properties of Naturally Occurring Polyether Antibiotics","volume":"2013","author":"Rutkowski","year":"2013","journal-title":"Biomed Res. Int."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1039\/a908607b","article-title":"Characterization of ionophore\u2013metal complexes by infrared multiphoton photodissociation and collision activated dissociation in a quadrupole ion trap mass spectrometer","volume":"125","author":"Shen","year":"2000","journal-title":"Analyst"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/clinids\/5.1.137","article-title":"Zinc and infection","volume":"5","author":"Sugarman","year":"1983","journal-title":"Rev. Infect. Dis."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"15992","DOI":"10.1002\/chem.201602376","article-title":"Zinc Homeostasis at the Bacteria\/Host Interface-From Coordination Chemistry to Nutritional Immunity","volume":"22","author":"Potocki","year":"2016","journal-title":"Chemistry"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.colsurfa.2014.05.057","article-title":"The contribution of zinc ions to the antimicrobial activity of zinc oxide","volume":"457","author":"Pasquet","year":"2014","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_181","first-page":"140","article-title":"Zinc Pyrithione: A Topical Antimicrobial with Complex Pharmaceutics","volume":"15","author":"Schwartz","year":"2016","journal-title":"J. Drugs Dermatol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1128\/mSphere.00194-16","article-title":"Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment","volume":"1","author":"Blanchard","year":"2016","journal-title":"mSphere"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"127110","DOI":"10.1016\/j.bmcl.2020.127110","article-title":"Substituted sulfonamide bioisosteres of 8-hydroxyquinoline as zinc-dependent antibacterial compounds","volume":"30","author":"McGowan","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1021\/ic0494051","article-title":"Clioquinol, a drug for Alzheimer\u2019s disease specifically interfering with brain metal metabolism: Structural characterization of its zinc(II) and copper(II) complexes","volume":"43","author":"Bazzicalupi","year":"2004","journal-title":"Inorg. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1039\/c3sc50882j","article-title":"Biological activity of synthetic ionophores: Ion transporters as prospective drugs?","volume":"4","author":"Alfonso","year":"2013","journal-title":"Chem. Sci."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1042\/BJ20081421","article-title":"Clioquinol targets zinc to lysosomes in human cancer cells","volume":"417","author":"Yu","year":"2009","journal-title":"Biochem. J."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/leu.2008.232","article-title":"Clioquinol inhibits the proteasome and displays preclinical activity in leukemia and myeloma","volume":"23","author":"Mao","year":"2009","journal-title":"Leukemia"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.canlet.2008.06.011","article-title":"Zinc-binding compounds induce cancer cell death via distinct modes of action","volume":"271","author":"Ding","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_189","unstructured":"Atala, A., and Lanza, R.P. (2002). Pesticides as Endocrine-Disrupting Chemicals. Methods of Tissue Engineering, Academic Press."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1016\/0006-2952(94)90586-X","article-title":"Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor \u03baB (NF-\u03baB) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes","volume":"48","author":"Bessho","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/ejic.201601120","article-title":"Structures of the Copper and Zinc Complexes of PBT2, a Chelating Agent Evaluated as Potential Drug for Neurodegenerative Diseases","volume":"2017","author":"Nguyen","year":"2017","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.neuron.2008.06.018","article-title":"Rapid Restoration of Cognition in Alzheimer\u2019s Transgenic Mice with 8-Hydroxy Quinoline Analogs Is Associated with Decreased Interstitial A\u03b2","volume":"59","author":"Adlard","year":"2008","journal-title":"Neuron"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S1474-4422(08)70167-4","article-title":"Safety, efficacy, and biomarker findings of PBT2 in targeting A\u03b2 as a modifying therapy for Alzheimer\u2019s disease: A phase IIa, double-blind, randomised, placebo-controlled trial","volume":"7","author":"Lannfelt","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_194","first-page":"5649","article-title":"Multiple Bactericidal Mechanisms of the Zinc Ionophore PBT2","volume":"5","author":"Ferguson","year":"2020","journal-title":"mSphere"},{"key":"ref_195","first-page":"1","article-title":"Zincophorin\u2013biosynthesis in Streptomyces griseus and antibiotic properties","volume":"4","author":"Walther","year":"2016","journal-title":"GMS Infect. Dis."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/B978-0-12-374419-7.00018-4","article-title":"Molecular Basis of Pulmonary Disease","volume":"417","author":"Farver","year":"2009","journal-title":"Mol. Pathol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1128\/JCM.00457-09","article-title":"Life-Threatening Infection Caused by Daptomycin-Resistant Corynebacterium jeikeium in a Neutropenic Patient","volume":"47","author":"Schoen","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1016\/j.febslet.2005.04.063","article-title":"Signaling pathways involved in tumor necrosis factor alpha-induced upregulation of the taurine transporter in Caco-2 cells","volume":"579","author":"Mochizuki","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1016\/j.ejmech.2010.01.059","article-title":"Synthesis and biological evaluation of some pyrazolylpyrazolines as anti-inflammatory\u2013antimicrobial agents","volume":"45","author":"Sharma","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1574-6968.2008.01069.x","article-title":"Antibacterial activity of pyrrolidine dithiocarbamate","volume":"280","author":"Kang","year":"2008","journal-title":"FEMS Microbiol. Lett."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/9\/228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:05:29Z","timestamp":1760177129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/9\/228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":200,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ph13090228"],"URL":"https:\/\/doi.org\/10.3390\/ph13090228","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}