Review Article

Facts and Myths: Efficacies of Repurposing Chloroquine and Hydroxychloroquine for the Treatment of COVID-19

Author(s): Abdul Alim Al-Bari*

Volume 21, Issue 16, 2020

Page: [1703 - 1721] Pages: 19

DOI: 10.2174/1389450121666200617133142

Price: $65

Abstract

The emergence of coronavirus disease 2019 (COVID-19) is caused by the 2019 novel coronavirus (2019-nCoV). The 2019-nCoV first broke out in Wuhan and subsequently spread worldwide owing to its extreme transmission efficiency. The fact that the COVID-19 cases and mortalities are reported globally and the WHO has declared this outbreak as the pandemic, the international health authorities have focused on rapid diagnosis and isolation of patients as well as search for therapies able to counter the disease severity. Due to the lack of known specific, effective and proven therapies as well as the situation of public-health emergency, drug repurposing appears to be the best armour to find a therapeutic solution against 2019-nCoV infection. Repurposing anti-malarial drugs and chloroquine (CQ)/ hydroxychloroquine (HCQ) have shown efficacy to inhibit most coronaviruses, including SARS-CoV-1 coronavirus. These CQ analogues have shown potential efficacy to inhibit 2019-nCoV in vitro that leads to focus several future clinical trials. This review discusses the possible effective roles and mechanisms of CQ analogues for interfering with the 2019-nCoV replication cycle and infection.

Keywords: 2019-nCoV, COVID-19, drug repurposing, hydroxychloroquine, clinical trials, pandemic.

Graphical Abstract
[1]
Adams MJ, Lefkowitz EJ, King AM, et al. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016). Arch Virol 2016; 161(10): 2921-49.
[http://dx.doi.org/10.1007/s00705-016-2977-6] [PMID: 27424026]
[2]
Perlman S, Netland J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 2009; 7(6): 439-50.
[http://dx.doi.org/10.1038/nrmicro2147] [PMID: 19430490]
[3]
Larson HE, Reed SE, Tyrrell DA. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Virol 1980; 5(3): 221-9.
[http://dx.doi.org/10.1002/jmv.1890050306] [PMID: 6262450]
[4]
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 2020.173104646
[http://dx.doi.org/10.1016/j.antiviral.2019.104646] [PMID: 31705922]
[5]
Arden KE, Nissen MD, Sloots TP, Mackay IM. New human coronavirus, HCoV-NL63, associated with severe lower respiratory tract disease in Australia. J Med Virol 2005; 75(3): 455-62.
[http://dx.doi.org/10.1002/jmv.20288] [PMID: 15648064]
[6]
van der Hoek L, Pyrc K, Jebbink MF, et al. Identification of a new human coronavirus. Nat Med 2004; 10(4): 368-73.
[http://dx.doi.org/10.1038/nm1024] [PMID: 15034574]
[7]
Woo PC, Lau SK, Tsoi HW, et al. Clinical and molecular epidemiological features of coronavirus HKU1-associated community-acquired pneumonia. J Infect Dis 2005; 192(11): 1898-907.
[http://dx.doi.org/10.1086/497151] [PMID: 16267760]
[8]
Ksiazek TG, Erdman D, Goldsmith CS, et al. SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003; 348(20): 1953-66.
[http://dx.doi.org/10.1056/NEJMoa030781] [PMID: 12690092]
[9]
Gralinski LE, Baric RS. Molecular pathology of emerging coronavirus infections. J Pathol 2015; 235(2): 185-95.
[http://dx.doi.org/10.1002/path.4454] [PMID: 25270030]
[10]
Milne-Price S, Miazgowicz KL, Munster VJ. The emergence of the Middle East respiratory syndrome coronavirus. Pathog Dis 2014; 71(2): 121-36.
[http://dx.doi.org/10.1111/2049-632X.12166] [PMID: 24585737]
[11]
Arabi YM, Harthi A, Hussein J, et al. Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV). Infection 2015; 43(4): 495-501.
[http://dx.doi.org/10.1007/s15010-015-0720-y] [PMID: 25600929]
[12]
Arbour N, Day R, Newcombe J, Talbot PJ. Neuroinvasion by human respiratory coronaviruses. J Virol 2000; 74(19): 8913-21.
[http://dx.doi.org/10.1128/JVI.74.19.8913-8921.2000] [PMID: 10982334]
[13]
Morfopoulou S, Brown JR, Davies EG, et al. Human coronavirus OC43 associated with fatal encephalitis. N Engl J Med 2016; 375(5): 497-8.
[http://dx.doi.org/10.1056/NEJMc1509458] [PMID: 27518687]
[14]
Koyuncu OO, Hogue IB, Enquist LW. Virus infections in the nervous system. Cell Host Microbe 2013; 13(4): 379-93.
[http://dx.doi.org/10.1016/j.chom.2013.03.010] [PMID: 23601101]
[15]
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.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[16]
Zhu N, Zhang D, Wang W, et al. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382(8): 727-33.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[17]
Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[18]
Lai C-C, Liu YH, Wang C-Y, et al. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths. J Microbiol Immunol Infect 2020; 53(3): 404-12.
[http://dx.doi.org/10.1016/j.jmii.2020.02.012] [PMID: 32173241]
[19]
Huang WH, Teng LC, Yeh TK, et al. novel coronavirus disease (COVID-19) in Taiwan: reports of two cases from Wuhan, China. J Microbiol Immunol Infect 2019; 2020(Feb): 19.
[http://dx.doi.org/10.1016/j.jmii.2020.02.009] [PMID: 32111449]
[20]
Liu YC, Liao CH, Chang CF, Chou CC, Lin Y-R. A locally transmitted case of SARS-CoV-2 infection in Taiwan. N Engl J Med 2020; 382(11): 1070-2.
[http://dx.doi.org/10.1056/NEJMc2001573] [PMID: 32050059]
[21]
Lee PI, Hsueh PR. Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV. J Microbiol Immunol Infect 2020; 53(3): 365-7.
[http://dx.doi.org/10.1016/j.jmii.2020.02.001] [PMID: 32035811]
[22]
WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020 2020.https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020
[23]
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 2020; 19(3): 149-50.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[24]
Al-Bari MAA. 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): 1608-21.
[http://dx.doi.org/10.1093/jac/dkv018] [PMID: 25693996]
[25]
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020; 57: 279-83.
[http://dx.doi.org/10.1016/j.jcrc.2020.03.005] [PMID: 32173110]
[26]
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis 2003; 3(11): 722-7.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[27]
Colson P, Rolain J-M, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents 2020; 55(3)105923
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105923] [PMID: 32070753]
[28]
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): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[29]
Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends 2020; 14(1): 69-71.
[http://dx.doi.org/10.5582/bst.2020.01020] [PMID: 31996494]
[30]
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): 72-3.
[http://dx.doi.org/10.5582/bst.2020.01047] [PMID: 32074550]
[31]
Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020; 55(4)105932
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105932] [PMID: 32145363]
[32]
Jie H, He H, Xi H, Zhi Z. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. 2020; 4(3): 185-8.
[http://dx.doi.org/10.3760/cma.j.issn.1001-0939.2020.03.009] [PMID: 32164085]
[33]
DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: New estimates of R&D costs. J Health Econ 2016; 47: 20-33.
[http://dx.doi.org/10.1016/j.jhealeco.2016.01.012] [PMID: 26928437]
[34]
The Pharmaceutical Journal. Return on investment falls for pharmaceutical industry PJ January 2017 online 2017. online
[http://dx.doi.org/10.1211/PJ.2017.20202146.]
[35]
Berndt ER, Nass D, Kleinrock M, Aitken M. Decline in economic returns from new drugs raises questions about sustaining innovations. Health Aff (Millwood) 2015; 34(2): 245-52.
[http://dx.doi.org/10.1377/hlthaff.2014.1029] [PMID: 25646104]
[36]
Hernandez JJ, Pryszlak M, Smith L, et al. Giving drugs a second chance: Overcoming regulatory and financial hurdles in repurposing approved drugs as cancer therapeutics. Front Oncol 2017; 7: 273.
[http://dx.doi.org/10.3389/fonc.2017.00273] [PMID: 29184849]
[37]
Abbruzzese C, Matteoni S, Signore M, et al. Drug repurposing for the treatment of glioblastoma multiforme. J Exp Clin Cancer Res 2017; 36(1): 169.
[http://dx.doi.org/10.1186/s13046-017-0642-x] [PMID: 29179732]
[38]
Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 2004; 3(8): 673-83.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[39]
Vazquez-Martin A, López-Bonetc E, Cufí S, et al. Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions. Drug Resist Updat 2011; 14(4-5): 212-23.
[http://dx.doi.org/10.1016/j.drup.2011.04.003] [PMID: 21600837]
[40]
Barrow E, Nicola AV, Liu J. Multiscale perspectives of virus entry via endocytosis. Virol J 2013; 10: 177.
[http://dx.doi.org/10.1186/1743-422X-10-177] [PMID: 23734580]
[41]
Devaux CA, Rolain J-M, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 2020; 55(5)105938
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[42]
Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun 2004; 323(1): 264-8.
[http://dx.doi.org/10.1016/j.bbrc.2004.08.085] [PMID: 15351731]
[43]
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
[http://dx.doi.org/10.1002/prp2.293] [PMID: 28596841]
[44]
Akpovwa H. Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity. Cell Biochem Funct 2016; 34(4): 191-6.
[http://dx.doi.org/10.1002/cbf.3182] [PMID: 27001679]
[45]
Yan Y, Zou Z, Sun Y, et al. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res 2013; 23(2): 300-2.
[http://dx.doi.org/10.1038/cr.2012.165] [PMID: 23208422]
[46]
Delogu I, de Lamballerie X. Chikungunya disease and chloroquine treatment. J Med Virol 2011; 83(6): 1058-9.
[http://dx.doi.org/10.1002/jmv.22019] [PMID: 21503920]
[47]
Farias KJ, Machado PR, de Almeida Junior RF, de Aquino AA, da Fonseca BA. Chloroquine interferes with dengue-2 virus replication in U937 cells. Microbiol Immunol 2014; 58(6): 318-26.
[http://dx.doi.org/10.1111/1348-0421.12154] [PMID: 24773578]
[48]
Ferraris O, Moroso M, Pernet O, et al. Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules. Antiviral Res 2015; 118: 75-81.
[http://dx.doi.org/10.1016/j.antiviral.2015.03.005] [PMID: 25796972]
[49]
Coombs K, Mann E, Edwards J, Brown DT. Effects of chloroquine and cytochalasin B on the infection of cells by Sindbis virus and vesicular stomatitis virus. J Virol 1981; 37(3): 1060-5.
[http://dx.doi.org/10.1128/JVI.37.3.1060-1065.1981] [PMID: 6262524]
[50]
Roques P, Thiberville S-D, Dupuis-Maguiraga L, et al. Paradoxical effect of chloroquine treatment in enhancing chikungunya virus infection. Viruses 2018; 10(5): 268.
[http://dx.doi.org/10.3390/v10050268] [PMID: 29772762]
[51]
De Lamballerie X, Boisson V, Reynier J-C, et al. On chikungunya acute infection and chloroquine treatment. Vector Borne Zoonotic Dis 2008; 8(6): 837-9.
[http://dx.doi.org/10.1089/vbz.2008.0049] [PMID: 18620511]
[52]
Chauhan A, Tikoo A. The enigma of the clandestine association between chloroquine and HIV-1 infection. HIV Med 2015; 16(10): 585-90.
[http://dx.doi.org/10.1111/hiv.12295] [PMID: 26238012]
[53]
Helal GK, Gad MA, Abd-Ellah MF, Eid MS. Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients. J Med Virol 2016; 88(12): 2170-8.
[http://dx.doi.org/10.1002/jmv.24575] [PMID: 27183377]
[54]
Peymani P, Yeganeh B, Sabour S, et al. New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial). Can J Physiol Pharmacol 2016; 94(6): 613-9.
[http://dx.doi.org/10.1139/cjpp-2015-0507] [PMID: 26998724]
[55]
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): 3416-21.
[http://dx.doi.org/10.1128/AAC.01509-08] [PMID: 19506054]
[56]
Li C, Zhu X, Ji X, et al. Chloroquine, a FDA-approved drug, prevents Zika virus infection and its associated congenital microcephaly in mice. EBioMedicine 2017; 24: 189-94.
[http://dx.doi.org/10.1016/j.ebiom.2017.09.034] [PMID: 29033372]
[57]
Vigerust DJ, McCullers JA. Chloroquine is effective against influenza A virus in vitro but not in vivo. Influenza Other Respir Viruses 2007; 1(5-6): 189-92.
[http://dx.doi.org/10.1111/j.1750-2659.2007.00027.x] [PMID: 19453426]
[58]
Tricou V, Minh NN, Van TP, et al. A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adults. PLoS Negl Trop Dis 2010; 4(8)e785
[http://dx.doi.org/10.1371/journal.pntd.0000785] [PMID: 20706626]
[59]
Kono M, Tatsumi K, Imai AM, Saito K, Kuriyama T, Shirasawa H. 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): 150-2.
[http://dx.doi.org/10.1016/j.antiviral.2007.10.011] [PMID: 18055026]
[60]
Shen L, Yang Y, Ye F, et al. Safe and sensitive antiviral screening platform based on recombinant human coronavirus OC43 expressing the luciferase reporter gene. Antimicrob Agents Chemother 2016; 60(9): 5492-503.
[http://dx.doi.org/10.1128/AAC.00814-16] [PMID: 27381385]
[61]
Takano T, Katoh Y, Doki T, Hohdatsu T. Effect of chloroquine on feline infectious peritonitis virus infection in vitro and in vivo. Antiviral Res 2013; 99(2): 100-7.
[http://dx.doi.org/10.1016/j.antiviral.2013.04.016] [PMID: 23648708]
[62]
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): 4875-84.
[http://dx.doi.org/10.1128/AAC.03011-14] [PMID: 24841269]
[63]
Mo Y, Fisher D. A review of treatment modalities for Middle East respiratory syndrome. J Antimicrob Chemother 2016; 71(12): 3340-50.
[http://dx.doi.org/10.1093/jac/dkw338] [PMID: 27585965]
[64]
Barnard DL, Day CW, Bailey K, et al. Evaluation of immunomodulators, interferons and known in vitro SARS-coV inhibitors for inhibition of SARS-coV replication in BALB/c mice. Antivir Chem Chemother 2006; 17(5): 275-84.
[http://dx.doi.org/10.1177/095632020601700505] [PMID: 17176632]
[65]
Burkard C, Verheije MH, Wicht O, et al. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner. PLoS Pathog 2014; 10(11)e1004502
[http://dx.doi.org/10.1371/journal.ppat.1004502] [PMID: 25375324]
[66]
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): 718-29.
[http://dx.doi.org/10.1038/nrneph.2011.150] [PMID: 22009248]
[67]
Abdulaziz N, Shah AR, McCune WJ. Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update. Curr Opin Rheumatol 2018; 30(3): 249-55.
[http://dx.doi.org/10.1097/BOR.0000000000000500] [PMID: 29517495]
[68]
Iglesias Cubero G, Rodriguez Reguero JJ, Rojo Ortega JM. Restrictive cardiomyopathy caused by chloroquine. Br Heart J 1993; 69(5): 451-2.
[http://dx.doi.org/10.1136/hrt.69.5.451] [PMID: 8518071]
[69]
Yang ZY, Huang Y, Ganesh L, et al. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J Virol 2004; 78(11): 5642-50.
[http://dx.doi.org/10.1128/JVI.78.11.5642-5650.2004] [PMID: 15140961]
[70]
Wang H, Yang P, Liu K, et al. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res 2008; 18(2): 290-301.
[http://dx.doi.org/10.1038/cr.2008.15] [PMID: 18227861]
[71]
Cassell S, Edwards J, Brown DT. Effects of lysosomotropic weak bases on infection of BHK-21 cells by Sindbis virus. J Virol 1984; 52(3): 857-64.
[http://dx.doi.org/10.1128/JVI.52.3.857-864.1984] [PMID: 6492263]
[72]
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.
[http://dx.doi.org/10.1016/j.ijantimicag.2007.05.015] [PMID: 17629679]
[73]
Al-Bari MAA. A current view of molecular dissection in autophagy machinery. J Physiol Biochem 2020; 76(3): 357-72.
[http://dx.doi.org/10.1007/s13105-020-00746-0] [PMID: 32451934]
[74]
Galluzzi L, Bravo-San Pedro JM, Levine B, Green DR, Kroemer G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov 2017; 16(7): 487-511.
[http://dx.doi.org/10.1038/nrd.2017.22] [PMID: 28529316]
[75]
Kaur J, Debnath J. Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol 2015; 16(8): 461-72.
[http://dx.doi.org/10.1038/nrm4024] [PMID: 26177004]
[76]
Rockel JS, Kapoor M. Autophagy: controlling cell fate in rheumatic diseases. Nat Rev Rheumatol 2017; 13(3): 193.
[http://dx.doi.org/10.1038/nrrheum.2017.17] [PMID: 28202917]
[77]
Saftig P, Klumperman J. Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol 2009; 10(9): 623-35.
[http://dx.doi.org/10.1038/nrm2745] [PMID: 19672277]
[78]
Ballabio A. The awesome lysosome. EMBO Mol Med 2016; 8(2): 73-6.
[http://dx.doi.org/10.15252/emmm.201505966] [PMID: 26787653]
[79]
Mauthe M, Orhon I, Rocchi C, et al. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy 2018; 14(8): 1435-55.
[http://dx.doi.org/10.1080/15548627.2018.1474314] [PMID: 29940786]
[80]
Pujals A, Favre L, Pioche-Durieu C, et al. Constitutive autophagy contributes to resistance to TP53-mediated apoptosis in Epstein-Barr virus-positive latency III B-cell lymphoproliferations. Autophagy 2015; 11(12): 2275-87.
[http://dx.doi.org/10.1080/15548627.2015.1115939] [PMID: 26565591]
[81]
Maclean KH, Dorsey FC, Cleveland JL, Kastan MB. Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. J Clin Invest 2008; 118(1): 79-88.
[http://dx.doi.org/10.1172/JCI33700] [PMID: 18097482]
[82]
Al-Bari MAA, Xu P. Molecular regulation of autophagy machinery by mTOR-dependent and -independent pathways. Ann N Y Acad Sci 2020; 1467(1): 3-20.
[http://dx.doi.org/10.1111/nyas.14305] [PMID: 31985829]
[83]
Briant L, Robert-Hebmann V, Acquaviva C, Pelchen-Matthews A, Marsh M, Devaux C. The protein tyrosine kinase p56lck is required for triggering NF-kappaB activation upon interaction of human immunodeficiency virus type 1 envelope glycoprotein gp120 with cell surface CD4. J Virol 1998; 72(7): 6207-14.
[http://dx.doi.org/10.1128/JVI.72.7.6207-6214.1998] [PMID: 9621091]
[84]
Seitz M, Valbracht J, Quach J, Lotz M. Gold sodium thiomalate and chloroquine inhibit cytokine production in monocytic THP-1 cells through distinct transcriptional and posttranslational mechanisms. J Clin Immunol 2003; 23(6): 477-84.
[http://dx.doi.org/10.1023/B:JOCI.0000010424.41475.17] [PMID: 15031635]
[85]
Schlesinger PH, Krogstad DJ, Herwaldt BL. Antimalarial agents: mechanisms of action. Antimicrob Agents Chemother 1988; 32(6): 793-8.
[http://dx.doi.org/10.1128/AAC.32.6.793] [PMID: 3046479]
[86]
Raines MF, Bhargava SK, Rosen ES. The blood-retinal barrier in chloroquine retinopathy. Invest Ophthalmol Vis Sci 1989; 30(8): 1726-31.
[PMID: 2759787]
[87]
Mavrikakis I, Sfikakis PP, Mavrikakis E, et al. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. Ophthalmology 2003; 110(7): 1321-6.
[http://dx.doi.org/10.1016/S0161-6420(03)00409-3] [PMID: 12867385]
[88]
Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69(1): 20-8.
[http://dx.doi.org/10.1136/ard.2008.101766] [PMID: 19103632]
[89]
Lamoureux F, Thomas C, Crafter C, et al. Blocked autophagy using lysosomotropic agents sensitizes resistant prostate tumor cells to the novel Akt inhibitor AZD5363. Clin Cancer Res 2013; 19(4): 833-44.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3114] [PMID: 23258740]
[90]
Marzi A, Reinheckel T, Feldmann H, Cathepsin B &L . are not required for ebola virus replication. PLoS Negl Trop Dis 2012; 6(12)e1923
[http://dx.doi.org/10.1371/journal.pntd.0001923] [PMID: 23236527]
[91]
Geisbert TW, Hensley LE, Larsen T, et al. Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol 2003; 163(6): 2347-70.
[http://dx.doi.org/10.1016/S0002-9440(10)63591-2] [PMID: 14633608]
[92]
Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis 2006; 6(2): 67-9.
[http://dx.doi.org/10.1016/S1473-3099(06)70361-9] [PMID: 16439323]
[93]
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[94]
Savarino A, Lucia MB, Rastrelli E, et al. Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors. J Acquir Immune Defic Syndr 2004; 35(3): 223-32.
[http://dx.doi.org/10.1097/00126334-200403010-00002] [PMID: 15076236]
[95]
Naarding MA, Baan E, Pollakis G, Paxton WA. Effect of chloroquine on reducing HIV-1 replication in vitro and the DC-SIGN mediated transfer of virus to CD4+ T-lymphocytes. Retrovirology 2007; 4: 6.
[http://dx.doi.org/10.1186/1742-4690-4-6] [PMID: 17263871]
[96]
Simmons G, Bertram S, Glowacka I, et al. Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion. Virology 2011; 413(2): 265-74.
[http://dx.doi.org/10.1016/j.virol.2011.02.020] [PMID: 21435673]
[97]
Lim JJ, Grinstein S, Roth Z. Diversity and versatility of phagocytosis: roles in innate immunity, tissue remodeling, and homeostasis. Front Cell Infect Microbiol 2017; 7: 191.
[http://dx.doi.org/10.3389/fcimb.2017.00191] [PMID: 28589095]
[98]
Chen D, Xie J, Fiskesund R, et al. Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype. Nat Commun 2018; 9(1): 873.
[http://dx.doi.org/10.1038/s41467-018-03225-9] [PMID: 29491374]
[99]
Li GG, Guo ZZ, Ma XF, et al. The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis. Dev Comp Immunol 2016; 59: 89-98.
[http://dx.doi.org/10.1016/j.dci.2016.01.010] [PMID: 26806760]
[100]
Alloatti A, Kotsias F, Magalhaes JG, Amigorena S. Dendritic cell maturation and cross-presentation: timing matters! Immunol Rev 2016; 272(1): 97-108.
[http://dx.doi.org/10.1111/imr.12432] [PMID: 27319345]
[101]
Lotteau V, Teyton L, Peleraux A, et al. Intracellular transport of class II MHC molecules directed by invariant chain. Nature 1990; 348(6302): 600-5.
[http://dx.doi.org/10.1038/348600a0] [PMID: 2250716]
[102]
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.
[http://dx.doi.org/10.1186/s13075-017-1393-y] [PMID: 28793932]
[103]
van den Borne BE, Dijkmans BA, de Rooij HH, le Cessie S, Verweij CL. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J Rheumatol 1997; 24(1): 55-60.
[PMID: 9002011]
[104]
Randolph VB, Winkler G, Stollar V. Acidotropic amines inhibit proteolytic processing of flavivirus prM protein. Virology 1990; 174(2): 450-8.
[http://dx.doi.org/10.1016/0042-6822(90)90099-D] [PMID: 2154882]
[105]
Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004; 303(5663): 1529-31.
[http://dx.doi.org/10.1126/science.1093616] [PMID: 14976261]
[106]
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): 658-62.
[http://dx.doi.org/10.1038/nature07405] [PMID: 18820679]
[107]
Kuznik A, Bencina M, Svajger U, Jeras M, Rozman B, Jerala R. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol 2011; 186(8): 4794-804.
[http://dx.doi.org/10.4049/jimmunol.1000702] [PMID: 21398612]
[108]
Häcker H, Mischak H, Miethke T, et al. CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J 1998; 17(21): 6230-40.
[http://dx.doi.org/10.1093/emboj/17.21.6230] [PMID: 9799232]
[109]
Vollmer J, Tluk S, Schmitz C, et al. Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8. J Exp Med 2005; 202(11): 1575-85.
[http://dx.doi.org/10.1084/jem.20051696] [PMID: 16330816]
[110]
An J, Woodward JJ, Sasaki T, Minie M, Elkon KB. Cutting edge: Antimalarial drugs inhibit IFN-β production through blockade of cyclic GMP-AMP synthase-DNA interaction. J Immunol 2015; 194(9): 4089-93.
[http://dx.doi.org/10.4049/jimmunol.1402793] [PMID: 25821216]
[111]
Martinson JA, Montoya CJ, Usuga X, Ronquillo R, Landay AL, Desai SN. Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation. Antimicrob Agents Chemother 2010; 54(2): 871-81.
[http://dx.doi.org/10.1128/AAC.01246-09] [PMID: 19949061]
[112]
Accapezzato D, Visco V, Francavilla V, et al. Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. J Exp Med 2005; 202(6): 817-28.
[http://dx.doi.org/10.1084/jem.20051106] [PMID: 16157687]
[113]
Geisbert TW, Strong JE, Feldmann H. Considerations in the use of nonhuman primate models of Ebola virus and Marburg virus infection. J Infect Dis 2015 Oct; 1212(Suppl. 2): S91-7.
[http://dx.doi.org/10.1093/infdis/jiv284.]
[114]
Yang Z, Delgado R, Xu L, et al. Distinct cellular interactions of secreted and transmembrane Ebola virus glycoproteins. Science 1998; 279(5353): 1034-7.
[http://dx.doi.org/10.1126/science.279.5353.1034] [PMID: 9461435]
[115]
Tracey KJ, Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Rev Med 1994; 45: 491-503.
[http://dx.doi.org/10.1146/annurev.med.45.1.491] [PMID: 8198398]
[116]
Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 2004; 75(2): 163-89.
[http://dx.doi.org/10.1189/jlb.0603252] [PMID: 14525967]
[117]
Baize S, Leroy EM, Georges AJ, et al. Inflammatory responses in Ebola virus-infected patients. Clin Exp Immunol 2002; 128(1): 163-8.
[http://dx.doi.org/10.1046/j.1365-2249.2002.01800.x] [PMID: 11982604]
[118]
Routy JP, Angel JB, Patel M, et al. Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy. HIV Med 2015; 16(1): 48-56.
[http://dx.doi.org/10.1111/hiv.12171] [PMID: 24889179]
[119]
Leroux-Roels G, Bourguignon P, Willekens J, et al. Immunogenicity and safety of a booster dose of an investigational adjuvanted polyprotein HIV-1 vaccine in healthy adults and effect of administration of chloroquine. Clin Vaccine Immunol 2014; 21(3): 302-11.
[http://dx.doi.org/10.1128/CVI.00617-13] [PMID: 24391139]
[120]
Murray SM, Down CM, Boulware DR, et al. Reduction of immune activation with chloroquine therapy during chronic HIV infection. J Virol 2010; 84(22): 12082-6.
[http://dx.doi.org/10.1128/JVI.01466-10] [PMID: 20844049]
[121]
Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology 2015; 12: 51.
[http://dx.doi.org/10.1186/s12977-015-0178-0] [PMID: 26084487]
[122]
Chen L, Liu HG, Liu W, et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia Zhonghua Jie He He Hu Xi Za Zhi 2020; 43(3): 203-8.
[http://dx.doi.org/10.3760/cma.j.issn.1001-0939.2020.03.013] [PMID: 32164089]
[123]
Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 2020; 395(10225): 683-4.
[http://dx.doi.org/10.1016/S0140-6736(20)30361-5] [PMID: 32122468]
[124]
Strand V, Ahadieh S, French J, et al. Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. Arthritis Res Ther 2015; 17: 362.
[http://dx.doi.org/10.1186/s13075-015-0880-2] [PMID: 26669566]
[125]
Klumperman J, Locker JK, Meijer A, Horzinek MC, Geuze HJ, Rottier PJ. Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding. J Virol 1994; 68(10): 6523-34.
[http://dx.doi.org/10.1128/JVI.68.10.6523-6534.1994] [PMID: 8083990]
[126]
Wang PH, Cheng Y. Increasing host cellular receptor-angiotensin converting enzyme 2 (ACE2) expression by coronavirus may facilitate 2019 nCoV infection. bioRxiv 2020; 6(4): 10.
[http://dx.doi.org/10.1101/2020.02.24.963348]
[127]
Li R, Qiao S, Zhang G. Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV. J Infect 2020; 80(4): 469-96.
[http://dx.doi.org/10.1016/j.jinf.2020.02.013] [PMID: 32092392]
[128]
Zhao Y, Zhao Z, Wang Y, et al. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv 2020.
[http://dx.doi.org/10.1101/2020.01.26.919985]
[129]
Glowacka I, Bertram S, Müller MA, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol 2011; 85(9): 4122-34.
[http://dx.doi.org/10.1128/JVI.02232-10] [PMID: 21325420]
[130]
Kwiek JJ, Haystead TA, Rudolph J. Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry 2004; 43(15): 4538-47.
[http://dx.doi.org/10.1021/bi035923w] [PMID: 15078100]
[131]
Varki A. Sialic acids as ligands in recognition phenomena. FASEB J 1997; 11(4): 248-55.
[http://dx.doi.org/10.1096/fasebj.11.4.9068613] [PMID: 9068613]
[132]
Olofsson S, Kumlin U, Dimock K, Arnberg N. Avian influenza and sialic acid receptors: more than meets the eye? Lancet Infect Dis 2005; 5(3): 184-8.
[http://dx.doi.org/10.1016/S1473-3099(05)70026-8] [PMID: 15766653]
[133]
Zeng Q, Langereis MA, van Vliet ALW, Huizinga EG, de Groot RJ. Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution. Proc Natl Acad Sci USA 2008; 105(26): 9065-9.
[http://dx.doi.org/10.1073/pnas.0800502105] [PMID: 18550812]
[134]
Bakkers MJG, Lang Y, Feitsma LJ, et al. Betacoronavirus adaptation to humans involved progressive loss of hemagglutinin-esterase lectin activity. Cell Host Microbe 2017; 21(3): 356-66.
[http://dx.doi.org/10.1016/j.chom.2017.02.008] [PMID: 28279346]
[135]
Hall EA, Ramsey JE, Peng Z, et al. Novel organometallic chloroquine derivative inhibits tumor growth. J Cell Biochem 2018; 119(7): 5921-33.
[http://dx.doi.org/10.1002/jcb.26787] [PMID: 29575007]
[136]
Jiang Y, Wong S, Chen F, Chang T, Lu H, Stenzel MH. Influencing selectivity to cancer cells with mixed nanoparticles prepared from albumin-polymer conjugates and block copolymers. Bioconjug Chem 2017; 28(4): 979-85.
[http://dx.doi.org/10.1021/acs.bioconjchem.6b00698] [PMID: 28263565]
[137]
Liu L, Hu F, Wang H, et al. Secreted protein acidic and rich in cysteine mediated biomimetic delivery of methotrexate by albumin-based nanomedicines for rheumatoid arthritis therapy. ACS Nano 2019; 13(5): 5036-48.
[http://dx.doi.org/10.1021/acsnano.9b01710] [PMID: 30978282]
[138]
Jiang Y, Liang M, Svejkar D, et al. Albumin-micelles via a one-pot technology platform for the delivery of drugs. Chem Commun (Camb) 2014 Jun; 1850(48): 6394-7.
[http://dx.doi.org/10.1039/c4cc00616j.]
[139]
Zinger A, Koren L, Adir O, et al. Collagenase nanoparticles enhance the penetration of drugs into pancreatic tumors. ACS Nano 2019; 13(10): 11008-21.
[http://dx.doi.org/10.1021/acsnano.9b02395] [PMID: 31503443]
[140]
Yang J, Wang F, Yuan H, et al. Recent advances in ultra-small fluorescent Au nanoclusters toward oncological research. Nanoscale 2019; 11(39): 17967-80.
[http://dx.doi.org/10.1039/C9NR04301B] [PMID: 31355833]
[141]
Patel S, Kim J, Herrera M, Mukherjee A, Kabanov AV, Sahay G. Brief update on endocytosis of nanomedicines. Adv Drug Deliv Rev 2019; 144: 90-111.
[http://dx.doi.org/10.1016/j.addr.2019.08.004] [PMID: 31419450]
[142]
Kwakye-Berko F, Meshnick SR. Binding of chloroquine to DNA. Mol Biochem Parasitol 1989; 35(1): 51-5.
[http://dx.doi.org/10.1016/0166-6851(89)90141-2] [PMID: 2761572]
[143]
Gautret P, Lagier J-C, 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 2020.105949105949
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]

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