Chloroquine use improves dengue-related symptoms

Borges, Marcos Carvalho; Castro, Luiza Antunes; da Fonseca, Benedito Antonio Lopes

One possible explanation for the antiviral effect of chloroquine could be related to the impairment of viral replication by raising the intracellular pH and thereby interfering with endosome-mediated viral entry. An increase in pH in acidic organelles, including endosomes, lysosomes and Golgi vesicles, leads to unwanted changes in the post-translational modifications of newly synthesised proteins, particularly the inhibition of glycosylation (Savarino et al. 2004 , Rolain et al. 2007 ). These effects are of particular importance in DENV infection because these viruses require endosomal acidification to release their viral RNA in the cytoplasm to initiate viral replication (Lindenbach & Rice 2003) . Other possible antiviral actions of chloroquine are based on either interference with the post-translational processing of viral glycoproteins, leading to imperfect glycosylation or to undefined interference with the late stages of viral replication (Savarino et al. 2003 (Savarino et al. , 2004 . However, the exact mechanism of action of chloroquine has not been completely elucidated and differs depending on different pathogens (Rolain et al. 2007 ). Tricou et al. (2010) evaluated the effect of chloroquine in hospitalised adult patients with dengue and found no difference in viraemia or NS1 antigenaemia duration and modest anti-pyretic activity for chloroquine in the intention-to-treat population, but not in dengue laboratory-confirmed cases. Moreover, these researchers observed a trend toward a lower incidence of dengue haemorrhagic fever in dengue patients treated with chloroquine.