Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells

Abstract

Dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV-2). Real-time RT-PCR and plaque assays were used to quantify the DENV-2 load in infected Vero and C6/36 cells after chloroquine treatment. Our results showed that a dose of 50 μg/ml of chloroquine was not toxic to the cells and induced a statistically significant inhibition of virus production in infected Vero cells when compared to untreated cells. In C6/36 cells, chloroquine does not induce a statistically significant difference in viral replication when compared to untreated cells, showing that this virus uses an unlikely pathway of penetration in these cells, and results were also confirmed by the plaque assay (PFU). These data suggest that the inhibition of virus infection induced by chloroquine is due to interference with acidic vesicles in mammalian cells.

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

“…The EC50 or concentration of chloroquine that protected 50% of the cells from ZIKV infection assessed by cell viability, was 9.82–14.2 μM depending on the cell model and the CC50 ranged from 94.95 to 134.54 μM (Table 1). The values of EC50 obtained for ZIKV MR766 are lower than those obtained for DENV inhibition (~25 μM) and HIV inhibition (100 μM) [20,22]. Furthermore, we observed similar ZIKV inhibitory effects of chloroquine when tested on different ZIKV lineage infections (Figure 2 and Figure 5), supporting the idea that chloroquine could help to manage recent infections caused by Asian ZIKV lineage.…”

“…It is approved by the Food and Drug Administration (FDA) to treat malaria and has long been prophylactically prescribed to pregnant women at risk of exposure to Plasmodium parasites [19]. Chloroquine, through the inhibition of pH-dependent steps of viral replication, restricts human immunodeficiency virus (HIV) [20], influenza virus [21], DENV [22], JEV [23], and WNV infection [24]. Here we investigated the antiviral effects of chloroquine on both Asian (using a Brazilian isolate) and African ZIKV infections in different cell types.…”

Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules

“…The antiviral efficacy of this molecule was shown on different cell culture with IC 50 related to each pathogens. Chloroquine was shown to inhibit Chikungunya virus (IC 50 10 lM) (Khan et al, 2010), Dengue virus (Farias et al, 2013), coronavirus (IC 50 8.8 lM) (Keyaerts et al, 2004), MERS-CoV (IC 50 3.0 lM) (De Wilde et al, 2014), influenza virus (IC 50 3.6 lM) (Ooi et al, 2006), or Henipavirus (IC 50 2 lM) (Porotto et al, 2009). Chloroquine was also used to inhibit HIV 1 in lineages of monocytes and lymphocytes (Sperber et al, 1993) which are Fig.…”

Chloroquine interferes with dengue‐2 virus replication in U937 cells

“…We demonstrate here the antiviral effect of CLQ on U937 cells infected with DENV‐2. Our findings are in agreement with those reported by Farias et al ., who showed that when Vero cells infected with DENV‐2 are treated with CLQ at 1 hr post‐infection and at different time intervals (24/12 hr), viral replication decreases in a dose dependent manner .…”