Antiviral Activity of Chloroquine Against Dengue Virus Type 2 Replication inAotusMonkeys

Abstract

Dengue virus (DENV) of the Flaviviridae family is a single positive-stranded RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The objective of this study was to investigate the use of chloroquine (CLQ) as an antiviral drug against dengue virus in monkeys. To analyze the action of the drug in vivo, nonhuman primates groups (Aotus azarai infulatus) were inoculated with a subcutaneous injection of a virulent strain of DENV-2, treated and untreated CLQ. Blood hematological, viremia, and serum biochemical values were obtained from 16 DENV-2-inoculated, treated and untreated; four received only CLQ and one mock-infected Aotus monkeys. Monkey serum samples (day 0-10 post-inoculation) were assayed by reverse transcription polymerase chain reaction and Cytometric Bead Array for determination of viremia and inflammatory cytokines, respectively. Additionally, body temperature and activity levels were determined. In the present work, CLQ was effective on replication of DENV-2 in Aotus monkeys; a time viremia reduction was observed compared with the controls. The concentration of tumor necrosis factor alpha and interferon gamma in the serum of the animals had a statistically significant reduction in the groups treated with CLQ after infection compared with the controls. A significant decrease in systemic levels of the liver enzyme aspartate aminotransferase (AST) was also observed in the animals treated with CLQ after infection compared with the controls. These results suggest that CLQ interferes in DENV-2 replication in Aotus monkeys.

Antiviral activity of cationic amphiphilic drugs

“…Two clinical trials specifically aimed at addressing chloroquine efficacy on acute phase of chikungunya virus infection were concluded with contrasting results [69]. On the other hand, chloroquine seems to be effective in vivo, at least in the mouse model, in inhibiting the human coronavirus subtype OC43 and EBOV [45,46], as well as in the Aotus monkeys, affecting the dengue virus type 2 replication [83].…”

The Role of Secretory Autophagy in Zika Virus Transfer through the Placental Barrier

“…Chloroquine and its derivative hydroxychloroquine are such alkalizers and are used clinically as anticancer drugs or antimalarial candidate medicines (Vakifahmetoglu-Norberg et al, 2015). Chloroquine had inhibitory effects on flavivirus replication in vitro and significantly decreased Dengue virus type 2 replication in Aotus monkeys (Farias et al, 2015), but it did not reduce the duration of viral infection in a human clinical trial and showed several adverse effects, primarily vomiting (Tricou et al, 2010). More importantly, chloroquine seems not to be related with the equilibrium between degradative autophagy and secretory autophagy (Figure 1 and Table 1).…”

Development of a SYBR green I-based quantitative RT-PCR for Ross River virus: Application in vector competence studies and antiviral drug evaluation

“…However in this study, only marginal protection was observed with chloroquine against RRV. Different inhibitory mechanisms of chloroquine involves prevention of viral endocytosis (Khan et al, 2010), decrease in concentration of cytokines like TNF-␣, IFN-␥ that are associated with disease severity and decrease in systemic levels of a liver enzyme (Aspartate aminotransferase) (Farias et al, 2015). In contrast, ribavirin, a broad spectrum antiviral inhibits inosine monophosphate dehydrogenase (IMPDH), thus depleting intracellular GTP pool (Takhampunya et al, 2006).…”

“…Ribavirin and Chloroquine are widely used antivirals for several families of viruses. Antiviral effect of chloroquine has been reported against several viruses including Chikungunya virus, Hepatitis C virus, Crimean-Congo Haemorrhagic fever virus, Human Immunodeficiency virus, Selmiki forest virus, SARS coronavirus (Khan et al, 2010;Farias et al, 2015;Helenius et al, 1982). Similarly, Ribavirin has been shown to inhibit Dengue virus, Chikungunya virus, Orthopoxviruses, Hantaan virus, Bornavirus, Canine Distemper virus etc (Smee et al, 2001;Takhampunya et al, 2006).…”