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7004433 
Journal Article 
Nanoviricides As Anti-Influenza Agents 
Diwan, AniR; Barton, RW; Tatake, JG; Menon, K; , 
2011 
CRC PRESS-TAYLOR & FRANCIS GROUP 
BOCA RATON 
163-166 
WOS:000394061000044 
Nanoviricides (R) anti-influenza agents are designed to mimic a natural host cell receptor to which all influenza A viruses bind and infect host cells. A nanoviricide is composed of a flexible polymer backbone with virus-specific ligands attached. The attachment of multiple ligands to a single polymer chain coupled with the fact that multiple polymer chains make up a single micelle leads to a very high avidity for the nanomicelle binding to the virus. A nanoviricide micelle may bind to a virus particle because of the specific interactions between the nanoviricide ligands and the glycoproteins on the virus surface. Binding of the influenza virus to the nanomicelle is believed to neutralize and engulf the virus, rendering it incapable of infection.Anti-influenza nanoviricides (R) were evaluated for efficacy and potency in vivo using a highly lethal model, allowing the survival lifetimes to be directly used for rank ordering of efficacy. One million virus particles of Influenza A Strain A/WS/33 (H1N1) were aspirated directly into the lungs of mice. A repeat "booster" infection was performed at 22 hrs. This influenza model was designed to be uniformly fatal in 100% of the infected, untreated animals within 5 days after infection. Treatment with both the anti-influenza nanoviricides and Tamiflu (Roche) commenced 24 hours after the first viral infection. Tamiflu was administered orally twice daily at 20mg/kg (i.e. 40mg/kg/day) while the anti-influenza nanoviricides were intravenous injections at 100mg/kg every 48 hrs. The animals treated with the best of the optimized, anti influenza nanoviricides survived greater than twice as long (18.1 days) as opposed to the animals treated with Tamiflu (7.8 days) The increased survival was associated with a reduction in lung viral load measured at 4 days after virus infection. The most effective anti-influenza agent tested demonstrated a greater than 15-fold greater viral load reduction as compared to Tamiflu. Thus, nanoviricides represent potential anti-influenza therapeutic agents with a novel mechanism of action; further optimization is in progress. 
Laudon, M; Romanowicz, B; 
978-1-4398-7138-6 
NSTI Nanotechnology Conference and Expo 
Boston, MA