[60] Nanotechnology has brought new options for hRSV treatment and prophylaxis,

using the anti-microbial activity of metals, such as silver and gold.[66] Although due to their toxicity, the clinical use of these metals in humans seems unfeasible, the development of silver or gold nanoparticles combined with polyvinylpyrrolidone have been shown to efficiently inhibit hRSV replication, showing low toxicity in cell CHIR-99021 nmr lines. Further, gold nanoparticles fused with inhibitor peptides displayed a high inhibitory capacity against hRSV.[66] Human RSV F protein nanoparticle vaccines have recently initiated clinical and preclinical studies to evaluate safety.[67] Another interesting therapeutic approach is the use of interference RNA that targets different steps during the hRSV infective cycle. The small interfering RNA (siRNA) strategy was initially used to target the expression of NS2[68] and the P[69] proteins, the latter showing an efficient capacity to protect mice against hRSV infection. This approach was also used to target the F gene, showing inhibition of hRSV

infection.[70] Nanotechnology has also been applied in combination with the siRNA approach to target the NS1 gene, resulting in the increase of IFN-β production by DCs and stimulated the Th1 differentiation of CD4+ cells.[71] Such a strategy protected mice against RSV infection, because treated mice showed decreased viral loads in lungs and

reduced inflammation in this tissue. Mitomycin C A new siRNA specific against NS1(ALN-RSV01) showed high antiviral activity that impaired nucleocapsid expression.[72] Studies in mice reported that administration of this molecule reduces RSV titres in the lungs.[73] This antiviral drug has also been evaluated in human clinical trials, demonstrating their safety and tolerance in healthy adults.[72] In addition, the effectiveness of ALN-RSV01 against hRSV infection was evaluated 5-Fluoracil mw in humans, with a 44% reduction of hRSV infection without adverse effects[74] and the phase IIb clinical trial has concluded. Further, this drug has been tested in lung transplant patients, where it has demonstrated safety and effectiveness.[74] Another strategy to combat the disease caused by hRSV is to target the harmful immune response elicited by hRSV infection. The exacerbated Th2 response associated with the hRSV bronchiolitis is characterized by high production of IL-4. Along these lines, a study generated an antisense oligomer to promote local silencing of il4 gene expression, which was delivered intranasally.[75] This approach was evaluated in neonatal murine models, showing a reduction of Th2 response and decreasing the airway damage caused by hRSV.[75] To improve the specificity of siRNA technology as an antiviral approach for hRSV, the use of phosphorodiamidatemorpholino oligomers (PMOs) has been proposed.