Repurposing of antiparasitic niclosamide to inhibit respiratory syncytial virus (RSV) replication

Despite being an important health problem, there are only supportive care treatments for respiratory syncytial virus (RSV) Infection. Thus, discovery of specific therapeutic drugs for RSV is still needed. Recently, an antiparasitic drug niclosamide has shown a broad-spectrum Antiviral activity. Here, our in vitro model was used to study the Antiviral effect of niclosamide on RSV and its related mechanism. Niclosamide inhibited RSV with time and dose-dependent manner. Pretreatment with submicromolar concentration of niclosamide for 6 h presented the highest anti-RSV activity of 94 % (50 % effective concentration; EC₅₀ of 0.022 μM). Niclosamide efficiently blocked Infection of laboratory strains and clinical isolates of both RSV-A and RSV-B in a bronchial epithelial cell line. Although a disruption of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by niclosamide was previously hypothesized as a mechanism against pH-independent viruses like RSV, using a chemical mTORC1 Inhibitor, temsirolimus, and a chemical mTORC1 agonist, MHY1485 (MHY), we show here that the mechanism of RSV inhibition by niclosamide was mTORC1 independent. Indeed, our data indicated that niclosamide hindered RSV Infection via proapoptotic activity by a reduction of Akt prosurvival protein, activation of cleaved Caspase-3 and PARP (poly ADP-ribose polymerase), and an early Apoptosis induction.