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

Delvecchio, Rodrigo; Higa, Luiza M.; Pezzuto, Paula; Valadão, Ana Luiza; Garcez, Patrícia P.; Monteiro, Fábio L.; Loiola, Erick C.; Dias, André A.; Silva, Fábio J. M.; Aliota, Matthew T.; Caine, Elizabeth A.; Osorio, Jorge E.; Bellio, Maria; O’Connor, David H.; Rehen, Stevens; de Aguiar, Renato Santana; Savarino, Andrea; Campanati, Loraine; Tanuri, Amilcar

Different mechanisms for the chloroquine inhibition of viral infection have been described [49] [50] [51] . We observed a strong reduction in the release of ZIKV particles when the drug was added at 0 h post-infection (Figure 3) , suggesting a higher impact on early stages of infection, possibly during fusion of the envelope protein to the endosome membrane. Chloroquine inhibits acidification of the endosome, consequently inhibiting the low pH-induced conformational changes required for the fusion of the envelope protein of flaviviruses with the endosomal membrane [52] . Chloroquine was also effective in decreasing virus release, although less pronouncedly and not statistically significant, when added after the early stages of virus infection (from 0.5 to 24 h post-infection), suggesting that later stages of the ZIKV replication cycle might also be affected (Figure 3) .