771. Novel Antiviral prevents Viral Upper Respiratory Infections in vitro and in vivo
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Background:

Respiratory viruses are responsible for substantial morbidity and mortality worldwide. Available prevention strategies are virus specific and have numerous shortcomings. Therefore, there is a need for development of new preventative antiviral strategies that offer a broad spectrum of protection.

ARMS-I is a first-in-class formulation that interrupts infection with a dual-action mechanism through 1) direct virucidal activity and 2) preventing contact between the virus and the host mucosal tissues through formation of a barrier.

Methods:

Virucidal activity and the barrier to infection were evaluated separately against medically important enveloped respiratory viruses including influenza A/B, RSV, and Parainfluenza. The effective concentration of ARMS-I was determined for each virus by TCID50 for 1) direct virucidal activity and 2) reduction in virus infectivity using cell overlay. The effect of ARMS-I on the morphology and ultrastructure of the viral envelope was determined using transmission electron microscopy. ARMS-1 treated, Oseltamvir treated and untreated C57/BL6 mice were infected intranasally with a lethal dose (LD50, 8.0 x 103 pfu/mouse) of a mouse-adapted influenza strain (PR8).  Mice body weights and survival were monitored daily for 14 days.

Results:

Effective concentration was determined to be  2% ARMS-I  (20ug/ml cetylpyridinium chloride) reducing viral titer by ≥2logs TCID50/ml.  Cells overlaid with as little as 27% of ARMS-I barrier components (94.5 mg/mL Glycerine; 1.08 mg/mL  xanthan gum) also exhibited ≥2log TCID50/ml decrease. TEM examination showed that ARMS-I disrupted the integrity of the viral envelope and its morphology. Survival data showed that 4 out of 10 untreated mice infected with influenza strain succumbed to the disease while no deaths in the ARMS-I – treated group of mice occurred.  There were no significant difference in survival between Arms1 or oseltamivir groups. ARMS-I treated mice exhibited higher average body weight compared to oseltamivir treated and untreated mice.

Conclusion:

ARMS-I  is effective in both disruption of  viral envelopes as well as prevention of viral invasion against numerous respiratory tract viruses. ARMS-I reduces influenza-associated mortality and morbidity in vivo.

Frank Esper, MD1, Matthew Dimaano, B.S.2, Daniel Popkin, MD, PhD2, Hisashi Fujioka, PhD3, Pranab Mukherjee, PhD4 and Mahmoud Ghannoum, PhD, FIDSA4, (1)Rainbow Babies and Children's Hospital, Cleveland, OH, (2)Case Western Reserve University, Cleveland, OH, (3)Department of Pharmacology, Case Western Reserve University, Cleveland, OH, (4)Case Western Reserve University/Center For Medical Mycology, Cleveland, OH

Disclosures:

F. Esper, None

M. Dimaano, None

D. Popkin, None

H. Fujioka, None

P. Mukherjee, ARMS pharmacutical: Consultant , Consulting fee and Research grant

M. Ghannoum, ARMS Pharmaceutical: Has a financial interest in ARMS Pharmaceutical , Consulting fee

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