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

Neuroprogenitor-enriched neurospheres, when subjected to differentiation culture conditions, can generate neurons. Our group recently demonstrated that ZIKV infection affected neurosphere size, neurite extension, and neuronal differentiation [34] . As we previously observed, neurospheres infected with ZIKV strain MR766 showed convoluted and misshapen neurites. Neurite extension was evaluated in chloroquine treated cultures by microtubule-associated protein 2 (Map2) staining and phase contrast microscopy and although many neurospheres were severely impacted by the infection, many others displayed the same general characteristics of mock-infected spheres indicating that chloroquine treatment rescued the neurite extension phenotype (Figure 6A-C) . Furthermore, ZIKV infection decreased when neurospheres were treated with 12.5 μM chloroquine, as evaluated by 4G2 staining (Figure 6D-F) . Data are represented as mean ± SD from two to three independent experiments. Statistical analysis was performed with Kruskal-Wallis test and multiple comparisons with infected and untreated control corrected by Dunn's test (* p < 0.05).