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Clinical features - Review

Advances in the use of chloroquine and hydroxychloroquine for the treatment of COVID-19

ORCID Icon, ORCID Icon, , , &
Pages 604-613 | Received 05 May 2020, Accepted 03 Jun 2020, Published online: 21 Jun 2020

References

  • Sahu KK, Mishra AK, Lal A. Novel coronavirus (2019-nCoV): update on 3rd coronavirus outbreak of 21st Century. QJM. 2020;113(5):384-386.
  • Haładyj E, Sikora M, Felis-Giemza A, et al. Antimalarials - are they effective and safe in rheumatic diseases? Reumatologia. 2018;56(3):164–173.
  • Al-Bari MA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother. 2015;70(6):1608–1621.
  • Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents. 2007;30(4):297–308.
  • Boelaert JR, Piette J, Sperber K. The potential place of chloroquine in the treatment of HIV-1-infected patients. J Clin Virol. 2001;20(3):137–140.
  • Tsiang H, Superti F. Ammonium chloride and chloroquine inhibit rabies virus infection in neuroblastoma cells. Brief Rep Arch Virol. 1984;81(3–4):377–382.
  • Kronenberger P, Vrijsen R, Boeyé A. Chloroquine induces empty capsid formation during poliovirus eclipse. J Virol. 1991;65(12):7008–7011.
  • Mizui T, Yamashina S, Tanida I, et al. Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J Gastroenterol. 2010;45(2):195–203.
  • Shah PP, Wang T, Kaletsky RL, et al. A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells. Mol Pharmacol. 2010;78(2):319–324.
  • de Wilde AH, Jochmans D, Posthuma CC, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014;58(8):4875–4884.
  • Biot C, Daher W, Chavain N, et al. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006;49(9):2845–2849.
  • Keyaerts E, Vijgen L, Maes P, et al. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004;323(1):264–268.
  • Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69.
  • Keyaerts E, Li S, Vijgen L, et al. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother. 2009;53(8):3416–3421.
  • Niu J, Shen L, Huang B, et al. Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice. Antiviral Res. 2020;173:104646.
  • Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269–271.
  • Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.
  • Yao X, Ye F, Zhang M, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa237.
  • Simmons G, Zmora P, Gierer S, et al. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Res. 2013;100(3):605–614.
  • Verma DK, Gupta D, Lal SK. Host lipid rafts play a major role in binding and endocytosis of influenza a virus. Viruses. 2018;10(11):650.
  • Lu Y, Liu DX, Tam JP. Lipid rafts are involved in SARS-CoV entry into Vero E6 cells. Biochem Biophys Res Commun. 2008;369(2):344–349.
  • Tortorici MA, Walls AC, Lang Y, et al. Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol. 2019;26(6):481–489.
  • Matrosovich M, Herrler G, Klenk HD. Sialic acid receptors of viruses. Top Curr Chem. 2015;367:1–28.
  • Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620.
  • Fantini J, Di Scala C, Chahinian H, et al. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int J Antimicrob Agents. 2020;55(5):105960.
  • Kwiek JJ, Haystead TA, Rudolph J. Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry. 2004;43(15):4538–4547.
  • Varki A. Sialic acids as ligands in recognition phenomena. Faseb J. 1997;11(4):248–255.
  • Heald-Sargent T, Gallagher T. Ready, set, fuse! The coronavirus spike protein and acquisition of fusion competence. Viruses. 2012;4(4):557–580.
  • Belouzard S, Millet JK, Licitra BN, et al. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses. 2012;4(6):1011–1033.
  • Millet JK, Whittaker GR. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015;202:120–134.
  • Gierer S, Bertram S, Kaup F, et al. The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies. J Virol. 2013;87(10):5502–5511.
  • Kawase M, Shirato K, Matsuyama S, et al. Protease-mediated entry via the endosome of human coronavirus 229E. J Virol. 2009;83(2):712–721.
  • Qiu Z, Hingley ST, Simmons G, et al. Endosomal proteolysis by cathepsins is necessary for murine coronavirus mouse hepatitis virus type 2 spike-mediated entry. J Virol. 2006;80(12):5768–5776.
  • Al-Bari MAA. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect. 2017;5(1):e00293.
  • Savarino A, Boelaert JR, Cassone A, et al. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis. 2003;3(11):722–727.
  • Banerjee S, Narayanan K, Mizutani T, et al. Murine coronavirus replication-induced p38 mitogen-activated protein kinase activation promotes interleukin-6 production and virus replication in cultured cells. J Virol. 2002;76(12):5937–5948.
  • Kopecky-Bromberg SA, Martinez-Sobrido L, Palese P. 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase. J Virol. 2006;80(2):785–793.
  • Kono M, Tatsumi K, Imai AM, et al. Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: involvement of p38 MAPK and ERK. Antiviral Res. 2008;77(2):150–152.
  • Wang LF, Lin YS, Huang NC, et al. Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015;35(3):143–156.
  • Lotteau V, Teyton L, Peleraux A, et al. Intracellular transport of class II MHC molecules directed by invariant chain. Nature. 1990;348(6302):600–605.
  • Wu SF, Chang CB, Hsu JM, et al. Hydroxychloroquine inhibits CD154 expression in CD4+ T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017;19(1):183.
  • Jang CH, Choi JH, Byun MS, et al. Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford). 2006;45(6):703–710.
  • Ewald SE, Lee BL, Lau L, et al. The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature. 2008;456(7222):658–662.
  • An J, Woodward JJ, Sasaki T, et al. Cutting edge: antimalarial drugs inhibit IFN-β production through blockade of cyclic GMP-AMP synthase-DNA interaction. J Immunol. 2015;194(9):4089–4093.
  • Löffler BM, Bohn E, Hesse B, et al. Effects of antimalarial drugs on phospholipase A and lysophospholipase activities in plasma membrane, mitochondrial, microsomal and cytosolic subcellular fractions of rat liver. Biochim Biophys Acta. 1985;835(3):448–455.
  • Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
  • Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
  • Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72–73.
  • Borba MGS, Val FFA, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a randomized clinical. JAMA Network Open. 2020;3(4):e208857.
  • Chen Z, Hu J, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv Preprint. 2020. DOI:10.1101/2020.03.22.20040758.
  • Rathi S, Lsh P, Kalantri A, et al. Hydroxychloroquine prophylaxis for COVID-19 contacts in India. Lancet Infect Dis. 2020. DOI:10.1016/S1473-3099(20)30313-3
  • Principi N, Esposito S. Chloroquine or hydroxychloroquine for prophylaxis of COVID-19. Lancet Infect Dis. 2020. DOI:10.1016/S1473-3099(20)30296-6
  • Mahévas M, Tran V-T, Roumier M, et al. No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen: results of a study using routinely collected data to emulate a target trial. medRxiv Preprint. 2020. DOI:10.1101/2020.04.10.20060699.
  • Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849.
  • Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with covid-19. N Engl J Med. 2020. DOI:10.1056/NEJMoa2012410.
  • Yu B, Li C, Chen P, et al. Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19. China Life Sci. 2020. DOI:10.1007/s11427-020-1732-2.
  • Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. DOI:10.1016/j.ijantimicag.2020.105949.
  • Gautret P, Lagier JC, Parola P, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis. 2020;34:101663.
  • Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv Preprint. 2020. DOI:10.1101/2020.04.16.20065920.
  • Rosenberg ES, Dufort EM, Udo T, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA. 2020. DOI:10.1001/jama.2020.8630.
  • Mehra MR, Desai SS, Ruschitzka F, et al. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020. DOI:10.1016/S0140-6736(20)31180-6
  • Garcia LS. Malaria. Clin Lab Med. 2010;30(1):93–129.
  • Good MI, Shader RI. Lethality and behavioral side effects of chloroquine. J Clin Psychopharmacol. 1982;2(1):40–47.
  • McChesney EW. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med. 1983;75(1A):11–18.
  • Jorge A, Ung C, Young LH, et al. Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018;14(12):693–703.
  • Lee SJ, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol. 2011;7(12):718–729.
  • Perinel S, Launay M, É B-N, et al. Towards optimization of hydroxychloroquine dosing in intensive care unit COVID-19 patients. Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa394.
  • Mercuro NJ, Yen CF, Shim DJ, et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020. DOI:10.1001/jamacardio.2020.1834.
  • Bessière F, Roccia H, Delinière A, et al. Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treatedwithhydroxychloroquinealone or in combination with azithromycin in an intensive care unit. JAMA Cardiol. 2020. DOI:10.1001/jamacardio.2020.1787.
  • Phru CS, Kibria MG, Thriemer K, et al. Case report: a case of primaquine-induced hemoglobinuria in glucose-6-phosphate dehydrogenase deficient malaria patient in Southeastern Bangladesh. Am J Trop Med Hyg. 2020;102(1):156–158.
  • Madrid PB, Chopra S, Manger ID, et al. A systematic screen of FDA-approved drugs for inhibitors of biological threat agents. PLoS One. 2013;8(4):e60579.
  • Dowall SD, Bosworth A, Watson R, et al. Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model. J Gen Virol. 2015;96(12):3484–3492.
  • Roques P, Thiberville SD, Dupuis-Maguiraga L, et al. Paradoxical effect of chloroquine treatment in enhancing chikungunya virus infection. Viruses. 2018;10(5):268.

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