First Author | Kumaki Y | Year | 2017 |
Journal | Antiviral Res | Volume | 139 |
Pages | 1-12 | PubMed ID | 27956136 |
Mgi Jnum | J:286953 | Mgi Id | MGI:6404250 |
Doi | 10.1016/j.antiviral.2016.12.007 | Citation | Kumaki Y, et al. (2017) Prophylactic and therapeutic intranasal administration with an immunomodulator, Hiltonol((R)) (Poly IC:LC), in a lethal SARS-CoV-infected BALB/c mouse model. Antiviral Res 139:1-12 |
abstractText | Hiltonol((R)), (Poly IC:LC), a potent immunomodulator, is a synthetic, double-stranded polyriboinosinic-polyribocytidylic acid (poly IC) stabilized with Poly-L-lysine and carboxymethyl cellulose (LC). Hiltonol((R)) was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. Hiltonol((R)) at 5, 1, 0.5 or 0.25 mg/kg/day by intranasal (i.n.) route resulted in significant survival benefit when administered at selected times 24 h prior to challenge with a lethal dose of mouse-adapted severe acute respiratory syndrome coronavirus (SARS-CoV). The infected BALB/c mice receiving the Hiltonol((R)) treatments were also significantly effective in protecting mice against weight loss due to infection (p < 0.001). Groups of 20 mice were dosed with Hiltonol((R)) at 2.5 or 0.75 mg/kg by intranasal instillation 7, 14, and 21 days before virus exposure and a second dose was given 24 h later, prophylactic Hiltonol((R)) treatments (2.5 mg/kg/day) were completely protective in preventing death, and in causing significant reduction in lung hemorrhage scores, lung weights and lung virus titers. Hiltonol((R)) was also effective as a therapeutic when give up to 8 h post virus exposure; 100% of the-infected mice were protected against death when Hiltonol((R)) was administered at 5 mg/kg/day 8 h after infection. Our data suggest that Hiltonol((R)) treatment of SARS-CoV infection in mice leads to substantial prophylactic and therapeutic effects and could be used for treatment of other virus disease such as those caused by MERS-CoV a related coronavirus. These properties might be therapeutically advantageous if Hiltonol((R)) is considered for possible clinical use. |