Chloroquine use improves dengue-related symptoms

Borges, Marcos C.; Castro, Luiza Antunes; Fonseca, Benedito Antônio Lopes da

doi:10.1590/s0074-02762013000500010

Cited by 81 publications

(69 citation statements)

References 24 publications

(30 reference statements)

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“…Two clinical trial studies of chloroquine have been conducted to assess chloroquine treatment in patients infected with DENV [37,38]. One of the trials evaluated the benefits of chloroquine treatment for 3 days in patients infected with DENV and showed no reduction in the duration or intensity of DENV viremia or nonstructural 1 protein (NS1) antigenemia clearance [37].…”

Section: Discussionmentioning

confidence: 99%

“…However, a trend towards a reduction in the number of dengue hemorrhagic fever cases was noticed in the chloroquine-treated group [37]. A more recent clinical trial of chloroquine administration to DENV-infected patients, also for 3 days, showed that 60% of the patients in the chloroquine-treated group reported feeling less pain and showed improvement in the performance of daily chores during treatment [38]. Moreover, the symptoms returned after medication withdrawal.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

Delvecchio

Higa

Pezzuto

et al. 2016

Viruses

234

195

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Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

Delvecchio

Higa

Pezzuto

et al. 2016

Viruses

234

195

View full text Add to dashboard Cite

show abstract

“…Two double-blind, randomized, placebo-controlled trials were performed with chloroquine, one in Vietnam and the other in Brazil. The first trial showed no significant impact on virological or immunological parameters of DENV infection in young adults [140], whereas the second study revealed that there was no significant difference in the duration of the disease or the degree and days of fever in DENV-infected patients treated with chloroquine compared with the control group [141]. Compounds with other mechanisms of action such as balapiravir, an inhibitor of viral polymerase and celgosivir, an iminosugar derivative that targets cellular endoplasmic reticulum α-glucosidases affecting viral glycoprotein processing, were also tested in clinical trials [142,143].…”

Section: • • Clinical Trials For Antiviral Compoundsmentioning

confidence: 92%

Dengue virus entry and trafficking: perspectives as antiviral target for prevention and therapy

2015

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Dengue virus (DENV) is the etiological agent of the most important human viral infection transmitted by mosquitoes in the world. In spite of the serious health threat that dengue represents, at present there are no vaccine or antiviral agents available and treatment of patients consists of supportive therapy. This review will focus on the process of DENV entry into the host cell as a potential target for antiviral therapy. The recent advances in the knowledge of viral and cellular molecules and mechanisms involved in binding, internalization and trafficking of DENV into the host cell until virion uncoating are discussed, together with an overview of the strategies and compounds evaluated for development of antiviral agents targeted to DENV entry. KeywordsDengue is currently the most widespread arbovirosis in the world, with a particularly high prevalence in diverse tropical and subtropical regions of America and Asia [1]. The WHO estimates an occurrence of 50-100 million annual infections, but more recent modelling evaluations increased the number of new possible infections to 390 million per year [2]. There are four serotypes of dengue viruses (DENV), designated DENV-1 to DENV-4, that cocirculate and are transmitted to humans by the bites of the mosquitoes Aedes aegypti and Aedes albopictus. Precisely, the failure in the programs for control of the mosquito vector is one of the reasons for the explosive re-emergence and global spread of dengue in the last few decades in >100 countries, resulting in a serious public health challenge.All serotypes can produce either an inapparent infection or a wide spectrum of clinical outcomes ranging from a mild febrile illness known as dengue fever (DF) to the more severe and life-threatening forms of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [3]. The initial infection with one DENV serotype leads to lifelong protection against homologous reinfection, but only brief and partial protection against infection with other serotypes. In fact, the secondary infection with a heterologous serotype is considered a risk factor for developing DHF and DSS. These severe clinical manifestations have been associated to the phenomenon known as antibody-dependent enhancement (ADE) [3]. In this process, the antibodies elicited by the primary infection bind to the heterotypic virus without neutralization of viral infectivity, and these immune complexes are opsonized into Fc-receptor positive cells leading to an increase in DENV replication and pathogenesis [4,5].DENV is a member of the genus Flavivirus in the family Flaviviridae. The virion is a small spherical particle, 40-50 nm in diameter, containing a single-stranded positive sense RNA included in an inner nucleocapsid and surrounded by a lipid envelope. The virus genome codes for a single polyprotein that is cleaved into three structural proteins (the capsid protein C,

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“…In fact many of those in the clinical phase are Data from the completed drug trials (Table 1) so far have not identified any promising drug candidate. Neither of the two CQ trials found any significant therapeutic benefit in CQtreated dengue patients [27,32]. One of these trials also demonstrated that NS1 clearance time may not be a reliable primary end-point, as NS1 persists even at the time of patient discharge from the hospital in many instances [32].…”

Section: Resultsmentioning

confidence: 99%

“…In parallel efforts, to accelerate the development of a drug for dengue, a handful of small molecules, being utilized/tested for other indications, have entered clinical trials for assessment of their utility for dengue therapy [27][28][29][30][31][32][33][34]. The small molecule drugs [35] in clinical trials are shown in Figure 1.…”

Section: Drugs In Clinical Developmentmentioning

confidence: 99%

Investigational drugs in early development for treating dengue infection

Beesetti

Khanna

Swaminathan

2016

Expert Opinion on Investigational Drugs

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None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

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Chloroquine use improves dengue-related symptoms

Cited by 81 publications

References 24 publications

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models

Dengue virus entry and trafficking: perspectives as antiviral target for prevention and therapy

Investigational drugs in early development for treating dengue infection

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