Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century

Jean-Marc Rolain, Philippe Colson, Didier Raoult, Jean-Marc Rolain, Philippe Colson, Didier Raoult

Abstract

Chloroquine (CQ) and its hydroxyl analogue hydroxychloroquine (HCQ) are weak bases with a half-century long use as antimalarial agents. Apart from this antimalarial activity, CQ and HCQ have gained interest in the field of other infectious diseases. One of the most interesting mechanisms of action is that CQ leads to alkalinisation of acid vesicles that inhibit the growth of several intracellular bacteria and fungi. The proof of concept of this effect was first used to restore intracellular pH allowing antibiotic efficacy for Coxiella burnetii, the agent of Q fever, and doxycycline plus HCQ is now the reference treatment for chronic Q fever. There is also strong evidence of a similar effect in vitro against Tropheryma whipplei, the agent of Whipple's disease, and a clinical trial is in progress. Other bacteria and fungi multiply in an acidic environment and encouraging in vitro data suggest that this concept may be generalised for all intracellular organisms that multiply in an acidic environment. For viruses, CQ led to inhibition of uncoating and/or alteration of post-translational modifications of newly synthesised proteins, especially inhibition of glycosylation. These effects have been well described in vitro for many viruses, with human immunodeficiency virus (HIV) being the most studied. Preliminary in vivo clinical trials suggest that CQ alone or in combination with antiretroviral drugs might represent an interesting way to treat HIV infection. In conclusion, our review re-emphasises the paradigm that activities mediated by lysosomotropic agents may offer an interesting weapon to face present and future infectious diseases worldwide.

Figures

Fig. 1
Fig. 1
Concept on the use of chloroquine (CQ) and hydroxychloroquine for intracellular bacteria and fungi: the Coxiella burnetii paradigm.
Fig. 2
Fig. 2
Strategy for replication of intracellular bacteria and fungi known to be inhibited by chloroquine and/or hydroxychloroquine.
Fig. 3
Fig. 3
Phagolysosomal alkalinisation and bactericidal effect of antibiotics (adapted from Maurin et al. [5]). Colours are those of universal colours used in pH paper. RVB, residual viable bacteria. [Awaiting permission from J Infect Dis.].
Fig. 4
Fig. 4
Viruses inhibited by chloroquine (CQ) and/or hydroxychloroquine (HCQ). HCV, hepatitis C virus; HAV, hepatitis A virus; HIV, human immunodeficiency virus; HSV-1, herpes simplex virus type-1; SARS-CoV, severe acute respiratory syndrome-associated coronavirus.

References

    1. Wellems T.E., Plowe C.V. Chloroquine-resistant malaria. J Infect Dis. 2001;184:770–776.
    1. Savarino A., Lucia M.B., Rastrelli E. Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors. J Acquir Immune Defic Syndr. 2004;35:223–232.
    1. O’Neill P.M., Bray P.G., Hawley S.R., Ward S.A., Park B.K. 4-Aminoquinolines—past, present, and future: a chemical perspective. Pharmacol Ther. 1998;77:29–58.
    1. Hackstadt T., Williams J.C. Biochemical stratagem for obligate parasitism of eukaryotic cells by Coxiella burnetii. Proc Natl Acad Sci USA. 1981;78:3240–3244.
    1. Maurin M., Benoliel A.M., Bongrand P., Raoult D. Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the Coxiella burnetii paradigm. J Infect Dis. 1992;166:1097–1102.
    1. Raoult D., Houpikian P., Tissot Dupont H., Riss J.M., Arditi-Djiane J., Brouqui P. Treatment of Q fever endocarditis: comparison of two regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med. 1999;159:167–173.
    1. Ghigo E., Capo C., Aurouze M. Survival of Tropheryma whipplei, the agent of Whipple's disease, requires phagosome acidification. Infect Immun. 2002;70:1501–1506.
    1. Boulos A., Rolain J.M., Raoult D. Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells. Antimicrob Agents Chemother. 2004;48:747–752.
    1. Maurin M., Raoult D. Optimum treatment of intracellular infection. Drugs. 1996;52:45–59.
    1. Maurin M., Raoult D. Intracellular organisms. Int J Antimicrob Agents. 1997;9:61–70.
    1. Byrd T.F., Horwitz M.A. Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. J Clin Invest. 1991;88:351–357.
    1. Fortier A.H., Leiby D.A., Narayanan R.B. Growth of Francisella tularensis LVS in macrophages: the acidic intracellular compartment provides essential iron required for growth. Infect Immun. 1995;63:1478–1483.
    1. Raoult D., Drancourt M., Vestris G. Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. Antimicrob Agents Chemother. 1990;34:1512–1514.
    1. Crowle A.J., May M.H. Inhibition of tubercle bacilli in cultured human macrophages by chloroquine used alone and in combination with streptomycin, isoniazid, pyrazinamide, and two metabolites of vitamin D3. Antimicrob Agents Chemother. 1990;34:2217–2222.
    1. Boelaert J.R., Appelberg R., Gomes M.S. Experimental results on chloroquine and AIDS-related opportunistic infections. J Acquir Immune Defic Syndr. 2001;26:300–301.
    1. Horowitz H., Carbonaro C.A. Inhibition of the Salmonella typhi oral vaccine strain, Ty21a, by mefloquine and chloroquine. J Infect Dis. 1992;166:1462–1464.
    1. Wiseman D. The effect of pH on the inhibitory activity of chloroquine against Escherichia coli. J Pharm Pharmacol. 1972;24(Suppl.):162P.
    1. Artenstein A.W., Opal S.M., Cristofaro P. Chloroquine enhances survival in Bacillus anthracis intoxication. J Infect Dis. 2004;190:1655–1660.
    1. Smith K.T., Dawes I.W. The preferential inhibition of Bacillus subtilis spore outgrowth by chloroquine. Arch Microbiol. 1989;152:251–257.
    1. Brorson O., Brorson S.H. An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine. Int Microbiol. 2002;5:25–31.
    1. Detilleux P.G., Deyoe B.L., Cheville N.F. Effect of endocytic and metabolic inhibitors on the internalization and intracellular growth of Brucella abortus in Vero cells. Am J Vet Res. 1991;52:1658–1664.
    1. Nguyen H.A., Grellet J., Paillard D., Dubois V., Quentin C., Saux M.C. Factors influencing the intracellular activity of fluoroquinolones: a study using levofloxacin in a Staphylococcus aureus THP-1 monocyte model. J Antimicrob Chemother. 2006;57:883–890.
    1. Prada-Delgado A., Carrasco-Marin E., Pena-Macarro C. Inhibition of Rab5a exchange activity is a key step for Listeria monocytogenes survival. Traffic. 2005;6:252–265.
    1. Newman S.L., Gootee L., Brunner G., Deepe G.S., Jr. Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis. J Clin Invest. 1994;93:1422–1429.
    1. Levitz S.M., Harrison T.S., Tabuni A., Liu X. Chloroquine induces human mononuclear phagocytes to inhibit and kill Cryptococcus neoformans by a mechanism independent of iron deprivation. J Clin Invest. 1997;100:1640–1646.
    1. Dias-Melicio FPetruzzielloL.A., Moreira A.P., Calvi S.A., Soares A.M. Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron. Microbiol Immunol. 2006;50:307–314.
    1. Taramelli D., Tognazioli C., Ravagnani F., Leopardi O., Giannulis G., Boelaert J.R. Inhibition of intramacrophage growth of Penicillium marneffei by 4-aminoquinolines. Antimicrob Agents Chemother. 2001;45:1450–1455.
    1. Jahn B., Langfelder K., Schneider U., Schindel C., Brakhage A.A. PKSP-dependent reduction of phagolysosome fusion and intracellular kill of Aspergillus fumigatus conidia by human monocyte-derived macrophages. Cell Microbiol. 2002;4:793–803.
    1. Sperber K., Kalb T.H., Stecher V.J., Banerjee R., Mayer L. Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes. AIDS Res Hum Retroviruses. 1993;9:91–98.
    1. Ferreira D.F., Santo M.P., Rebello M.A., Rebello M.C. Weak bases affect late stages of Mayaro virus replication cycle in vertebrate cells. J. Med. Microbiol. 2000;49(4):313–318.
    1. Pardridge W.M., Yang J., Diagne A. Chloroquine inhibits HIV-1 replication in human peripheral blood lymphocytes. Immunol Lett. 1998;64:45–47.
    1. Chiang G., Sassaroli M., Louie M., Chen H., Stecher V.J., Sperber K. Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine. Clin Ther. 1996;18:1080–1092.
    1. Vincent M.J., Bergeron E., Benjannet S. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69.
    1. Keyaerts E., Vijgen L., Maes P., Neyts J., Van R.M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004;323:264–268.
    1. Shibata M., Aoki H., Tsurumi T. Mechanism of uncoating of influenza B virus in MDCK cells: action of chloroquine. J Gen Virol. 1983;64:1149–1156.
    1. Savarino A., Di T.L., Donatelli I., Cauda R., Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis. 2006;6:67–69.
    1. Miller D.K., Lenard J. Antihistaminics, local anesthetics, and other amines as antiviral agents. Proc Natl Acad Sci USA. 1981;78:3605–3609.
    1. Ooi E.E., Chew J.S., Loh J.P., Chua R.C. In vitro inhibition of human influenza A virus replication by chloroquine. Virol J. 2006;3:39.
    1. Randolph V.B., Winkler G., Stollar V. Acidotropic amines inhibit proteolytic processing of flavivirus prM protein. Virology. 1990;174:450–458.
    1. Petruzziello R., Orsi N., Macchia S., Rieti S., Frey T.K., Mastromarino P. Pathway of rubella virus infectious entry into Vero cells. J Gen Virol. 1996;77(Pt 2):303–308.
    1. Nakhasi H.L., Zheng D., Callahan L., Dave J.R., Liu T.Y. Rubella virus: mechanism of attenuation in the vaccine strain (HPV77) Virus Res. 1989;13(3):231–243.
    1. Bishop N.E. Examination of potential inhibitors of hepatitis A virus uncoating. Intervirology. 1998;41:261–271.
    1. Offensperger W.B., Offensperger S., Walter E., Blum H.E., Gerok W. Inhibition of duck hepatitis B virus infection by lysosomotropic agents. Virology. 1991;183:415–418.
    1. Civitico G., Wang Y.Y., Luscombe C. Antiviral strategies in chronic hepatitis B virus infection: II. Inhibition of duck hepatitis B virus in vitro using conventional antiviral agents and supercoiled-DNA active compounds. J Med Virol. 1990;31:90–97.
    1. Blanchard E., Belouzard S., Goueslain L. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol. 2006;80:6964–6972.
    1. Glushakova S.E., Lukashevich I.S. Early events in arenavirus replication are sensitive to lysosomotropic compounds. Arch Virol. 1989;104:157–161.
    1. Borrow P., Oldstone M.B. Mechanism of lymphocytic choriomeningitis virus entry into cells. Virology. 1994;198(1):1–9.
    1. Tsiang H., Superti F. Ammonium chloride and chloroquine inhibit rabies virus infection in neuroblastoma cells Brief report. Arch Virol. 1984;81:377–382.
    1. Pontesilli O., Carotenuto P., Levin M.J., Suez D., Hayward A.R. Processing and presentation of cell-associated varicella–zoster virus antigens by human monocytes. Clin Exp Immunol. 1987;70:127–135.
    1. Lindemans C.A., Coffer P.J., Schellens I.M., de Graaff P.M., Kimpen J.L., Koenderman L. Respiratory syncytial virus inhibits granulocyte apoptosis through a phosphatidylinositol 3-kinase and NF-κB-dependent mechanism. J Immunol. 2006;176:5529–5537.
    1. Cassell S., Edwards J., Brown D.T. Effects of lysosomotropic weak bases on infection of BHK-21 cells by Sindbis virus. J Virol. 1984;52:857–864.
    1. Singh A.K., Sidhu G.S., Friedman R.M., Maheshwari R.K. Mechanism of enhancement of the antiviral action of interferon against herpes simplex virus-1 by chloroquine. J Interferon Cytokine Res. 1996;16:725–731.
    1. Koyama A.H., Uchida T. Inhibition of multiplication of herpes simplex virus type 1 by ammonium chloride and chloroquine. Virology. 1984;138(2):332–335.
    1. Miller N., Hutt-Fletcher L.M. Epstein–Barr virus enters B cells and epithelial cells by different routes. J Virol. 1992;66:3409–3414.
    1. Zeichhardt H., Wetz K., Willingmann P., Habermehl K.O. Entry of poliovirus type 1 and Mouse Elberfeld (ME) virus into HEp-2 cells: receptor-mediated endocytosis and endosomal or lysosomal uncoating. J Gen Virol. 1985;66:483–492.
    1. Kronenberger P., Vrijsen R., Boeye A. Chloroquine induces empty capsid formation during poliovirus eclipse. J Virol. 1991;65:7008–7011.
    1. Madshus I.H., Olsnes S., Sandvig K. Mechanism of entry into the cytosol of poliovirus type 1: requirement for low pH. J Cell Biol. 1984;98(4):1194–1200.
    1. Yoshida T., Takao S., Kiyotani K., Sakaguchi T. Endoproteolytic activation of Newcastle disease virus fusion proteins requires an intracellular acidic environment. Virology. 1989;170:571–574.
    1. Gonzalez-Dunia D., Cubitt B., de la Torre J.C. Mechanism of Borna disease virus entry into cells. J Virol. 1998;72:783–788.
    1. Miller D.K., Lenard J. Inhibition of vesicular stomatitis virus infection by spike glycoprotein. Evidence for an intracellular, G protein-requiring step. J Cell Biol. 1980;84(2):430–437.
    1. Fredericksen B.L., Whitt M.A. Attenuation of recombinant vesicular stomatitis viruses encoding mutant glycoproteins demonstrate a critical role for maintaining a high pH threshold for membrane fusion in viral fitness. Virology. 1998;240:349–358.
    1. Dille B.J., Johnson T.C. Inhibition of vesicular stomatitis virus glycoprotein expression by chloroquine. J Gen Virol. 1982;62:91–103.
    1. Janeczko R.A., Rodriguez J.F., Esteban M. Studies on the mechanism of entry of vaccinia virus in animal cells. Arch Virol. 1987;92:135–150.
    1. Pazmino N.H., Yuhas J.M., Tennant R.W. Inhibition of murine RNA tumor virus replication and oncogenesis by chloroquine. Int J Cancer. 1974;14:379–385.
    1. Carrillo E.C., Giachetti C., Campos R. Early steps in FMDV replication: further analysis on the effects of chloroquine. Virology. 1985;147:118–125.
    1. Ferreira D.F., Santo M.P., Rebello M.A., Rebello M.C. Weak bases affect late stages of Mayaro virus replication cycle in vertebrate cells. J Med Microbiol. 2000;49:313–318.
    1. Stuart A.D., Brown T.D. Entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes. J Virol. 2006;80:7500–7509.
    1. Geraldes A., Valdeira M.L. Effect of chloroquine on African swine fever virus infection. J Gen Virol. 1985;66(Pt 5):1145–1148.
    1. Mager A., Masengo R., Mammerickx M., Letesson J.J. T cell proliferative response to bovine leukaemia virus (BLV): identification of T cell epitopes on the major core protein (p24) in BLV-infected cattle with normal haematological values. J Gen Virol. 1994;75:2223–2231.
    1. Basak S., Turner H. Infectious entry pathway for canine parvovirus. Virology. 1992;186:368–376.
    1. Ros C., Burckhardt C.J., Kempf C. Cytoplasmic trafficking of minute virus of mice: low-pH requirement, routing to late endosomes, and proteasome interaction. J Virol. 2002;76(24):12634–12645.
    1. Hackstadt T., Williams J.C. pH dependence of the Coxiella burnetii glutamate transport system. J Bacteriol. 1983;154:598–603.
    1. Mege J.L., Maurin M., Capo C., Raoult D. Coxiella burnetii: the ‘query’ fever bacterium. A model of immune subversion by a strictly intracellular microorganism. FEMS Microbiol Rev. 1997;19:209–217.
    1. Maurin M., Raoult D. Q fever. Clin Microbiol Rev. 1999;12:518–553.
    1. Fenollar F., Fournier P.E., Carrieri M.P., Habib G., Messana T., Raoult D. Risks factors and prevention of Q fever endocarditis. Clin Infect Dis. 2001;33:312–316.
    1. Madariaga M.G., Pulvirenti J., Sekosan M., Paddock C.D., Zaki S.R. Q fever endocarditis in HIV-infected patient. Emerg Infect Dis. 2004;10:501–504.
    1. Senn L., Franciolli M., Raoult D. Coxiella burnetii vascular graft infection. BMC Infect Dis. 2005;5:109.
    1. Fenollar F., Thuny F., Xeridat B., Lepidi H., Raoult D. Endocarditis after acute Q fever in patients with previously undiagnosed valvulopathies. Clin Infect Dis. 2006;42:818–821.
    1. Landais C., Fenollar F., Thuny F., Raoult D. From acute Q fever to endocarditis: serological follow-up strategy. Clin Infect Dis. 2007;44:1337–1340.
    1. Landais C., Fenollar F., Constantin A. Q fever osteoarticular infection: four new cases and a review of the literature. Eur J Clin Microbiol Infect Dis. 2007;26:341–347.
    1. Raoult D., Birg M.L., La Scola B. Cultivation of the bacillus of Whipple's disease. New Engl J Med. 2000;342:620–625.
    1. Fenollar F., Puechal X., Raoult D. Whipple's disease. New Engl J Med. 2007;256:55–66.
    1. Rogers D.E., Tompsett R. The survival of staphylococci within human leukocytes. J Exp Med. 1952;95:209–230.
    1. Kapral F.A., Shayegani M.G. Intracellular survival of staphylococci. J Exp Med. 1959;110:123.
    1. Craven N., Williams M.R., Field T.R., Bunch K.J., Mayer S.J., Bourne S.J. The influence of extracellular and phagolysosomal pH changes on the bactericidal activity of bovine neutrophils against Staphylococcus aureus. Vet Immunol Immunopathol. 1986;13:97–110.
    1. Styrt B., Klempner M.S. Modification of interactions between neutrophils and staphylococci by lysosomotropic week bases. Infect Immun. 1985;50:415–419.
    1. Yancey R.J., Sanchez M.S., Ford C.W. Activity of antibiotics against Staphylococcus aureus within polymorphonuclear neutrophils. Eur J Clin Microbiol Infect Dis. 1991;10:107–113.
    1. Lam C., Mathison G.E. Effect of low intraphagolysosomal pH on antimicrobial activity of antibiotics against ingested staphylococci. J Med Microbiol. 1983;16:309–316.
    1. Maurin M., Raoult D. Phagolysosomal alkalinization and intracellular killing of Staphylococcus aureus by amikacin. J Infect Dis. 1994;169:330–336.
    1. Nguyen H.A., Grellet J., Dubois V., Saux M.C., Quentin C. Factors compromising the activity of moxifloxacin against intracellular Staphylococcus aureus. J Antimicrob Chemother. 2007;59:755–758.
    1. Sanchez M.S., Ford C.W., Yancey R.J., Jr. Evaluation of antibiotic effectiveness against Staphylococcus aureus surviving within the bovine mammary gland macrophage. J Antimicrob Chemother. 1988;21:773–786.
    1. Tulkens P.M. Intracellular distribution and activity of antibiotics. Eur J Clin Microbiol Infect Dis. 1991;10:100–106.
    1. Mandell G.L., Vest T.K. Killing of intraleukocytic Staphylococcus aureus by rifampin: in vitro and in vivo studies. J Infect Dis. 1972;125:486–490.
    1. Stout J.E., Yu V.L. Legionellosis. N Engl J Med. 1997;337:682–687.
    1. Weber S.M., Levitz S.M., Harrison T.S. Chloroquine and the fungal phagosome. Curr Opin Microbiol. 2000;3:349–353.
    1. Harrison T.S., Chen J., Simons E., Levitz S.M. Determination of the pH of the Cryptococcus neoformans vacuole. Med Mycol. 2002;40:329–332.
    1. Eissenberg L.G., Goldman W.E., Schlesinger P.H. Histoplasma capsulatum modulates the acidification of phagolysosomes. J Exp Med. 1995;177:1605–1611.
    1. Strasser J.E., Newman S.L., Ciraolo G.M., Morris R.E., Howell M.L., Dean G.E. Regulation of the macrophage vacuolar ATPase and phagosome–lysosome fusion by Histoplasma capsulatum. J Immunol. 1999;162:6148–6154.
    1. Schafer M.P., Dean G.E. Cloning and sequence analysis of an H(+)-ATPase-encoding gene from the human dimorphic pathogen Histoplasma capsulatum. Gene. 1993;136:295–300.
    1. Levitz S.M., Nong S.H., Seetoo K.F., Harrison T.S., Speizer R.A., Simons E.R. Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages. Infect Immun. 1999;67:885–890.
    1. Sieczkarski S.B., Whittaker G.R. Dissecting virus entry via endocytosis. J Gen Virol. 2002;83:1535–1545.
    1. Naarding M.A., Baan E., Pollakis G., Paxton W.A. 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.
    1. Kwiek J.J., Haystead T.A., Rudolph J. Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry. 2004;43:4538–4547.
    1. Ducharme J., Farinotti R. Clinical pharmacokinetics and metabolism of chloroquine. Focus on recent advancements. Clin Pharmacokinet. 1996;31:257–274.
    1. Boelaert J.R., Sperber K., Piette J. The additive in vitro anti-HIV-1 effect of chloroquine, when combined with zidovudine and hydroxyurea. Biochem Pharmacol. 2001;61:1531–1535.
    1. Witvrouw M., Pannecouque C., Switzer W.M., Folks T.M., De C.E., Heneine W. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther. 2004;9:57–65.
    1. Sperber K., Louie M., Kraus T. Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1. Clin Ther. 1995;17:622–636.
    1. Sperber K., Chiang G., Chen H. Comparison of hydroxychloroquine with zidovudine in asymptomatic patients infected with human immunodeficiency virus type 1. Clin Ther. 1997;19:913–923.
    1. Paton N.I., Aboulhab J., Karim F. Hydroxychloroquine, hydroxycarbamide, and didanosine as economic treatment for HIV-1. Lancet. 2002;359:1667–1668.
    1. Paton N.I., Aboulhab J. Hydroxychloroquine, hydroxyurea and didanosine as initial therapy for HIV-infected patients with low viral load: safety, efficacy and resistance profile after 144 weeks. HIV Med. 2005;6:13–20.
    1. Joshi S.R., Butala N., Patwardhan M.R., Daver N.G., Kelkar D. Low cost anti-retroviral options: chloroquine based ARV regimen combined with hydroxyurea and lamivudine: a new economical triple therapy. J Assoc Physicians India. 2004;52:597–598.
    1. Engchanil C., Kosalaraksa P., Lumbiganon P. Therapeutic potential of chloroquine added to zidovudine plus didanosine for HIV-1 infected children. J Med Assoc Thai. 2006;89:1229–1236.
    1. Kourtis A.P., Lee F.K., Abrams E.J., Jamieson D.J., Bulterys M. Mother-to-child transmission of HIV-1: timing and implications for prevention. Lancet Infect Dis. 2006;6:726–732.
    1. Savarino A., Boelaert J.R., Cassone A., Majori G., Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003;3:722–727.
    1. Malaty L.I., Kuper J.J. Drug interactions of HIV protease inhibitors. Drug Saf. 1999;20(2):147–169.
    1. Projean D., Baune B., Farinotti R. In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation. Drug Metab Dispos. 2003;31:748–754.
    1. Li W., Moore M.J., Vasilieva N. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454.
    1. Gallagher T.M., Escarmis C., Buchmeier M.J. Alteration of the pH dependence of coronavirus-induced cell fusion: effect of mutations in the spike glycoprotein. J Virol. 1991;65:1916–1928.
    1. Simmons G., Reeves J.D., Rennekamp A.J., Amberg S.M., Piefer A.J., Bates P. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. Proc Natl Acad Sci USA. 2004;101:4240–4245.
    1. Yang Z.Y., Huang Y., Ganesh L. 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;78:5642–5650.
    1. Biot C., Daher W., Chavain N. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006;49:2845–2849.
    1. Yoshimura A., Kuroda K., Kawasaki K., Yamashina S., Maeda T., Ohnishi S. Infectious cell entry mechanism of influenza virus. J Virol. 1982;43:284–293.
    1. Hirschman S.Z., Garfinkel E. Inhibition of hepatitis B DNA polymerase by intercalating agents. Nature. 1978;271:681–683.
    1. Hagelstein J., Fathinejad F., Stremmel W., Galle P.R. pH-independent uptake of hepatitis B virus in primary human hepatocytes. Virology. 1997;229:292–294.
    1. Kouroumalis E.A., Koskinas J. Treatment of chronic active hepatitis B (CAH B) with chloroquine: a preliminary report. Ann Acad Med Singapore. 1986;15:149–152.
    1. Accapezzato D., Visco V., Francavilla V. Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. J Exp Med. 2005;202:817–828.
    1. Rolain J.M., Mallet M.N., Raoult D. Correlation between serum levels of doxycycline and serology evolution in patients treated for Coxiella burnetii endocarditis. J Infect Dis. 2003;9:1322–1325.
    1. Rolain J.M., Boulos A., Mallet M.N., Raoult D. Correlation between ratio of serum doxycycline concentration to MIC and rapid decline of antibody levels during treatment of Q fever endocarditis. Antimicrob Agents Chemother. 2005;49:2673–2676.
    1. Klinger G., Morad Y., Westall C.A. Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet. 2001;358:813–814.
    1. Bernstein H.N. Ophthalmologic considerations and testing in patients receiving long-term antimalarial therapy. Am J Med. 1983;75:25–34.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa