We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro.
- Authors
Smith, Todd G.; Jackson, Felix R.; Morgan, Clint N.; Carson, William C.; Martin, Brock E.; Gallardo-Romero, Nadia; Ellison, James A.; Greenberg, Lauren; Hodge, Thomas; Squiquera, Luis; Sulley, Jamie; Olson, Victoria A.; Hutson, Christina L.
- Abstract
Currently, no rabies virus-specific antiviral drugs are available. Ranpirnase has strong antitumor and antiviral properties associated with its ribonuclease activity. TMR-001, a proprietary bulk drug substance solution of ranpirnase, was evaluated against rabies virus in three cell types: mouse neuroblastoma, BSR (baby hamster kidney cells), and bat primary fibroblast cells. When TMR-001 was added to cell monolayers 24 h preinfection, rabies virus release was inhibited for all cell types at three time points postinfection. TMR-001 treatment simultaneous with infection and 24 h postinfection effectively inhibited rabies virus release in the supernatant and cell-to-cell spread with 50% inhibitory concentrations of 0.2–2 nM and 20–600 nM, respectively. TMR-001 was administered at 0.1 mg/kg via intraperitoneal, intramuscular, or intravenous routes to Syrian hamsters beginning 24 h before a lethal rabies virus challenge and continuing once per day for up to 10 days. TMR-001 at this dose, formulation, and route of delivery did not prevent rabies virus transit from the periphery to the central nervous system in this model (n = 32). Further aspects of local controlled delivery of other active formulations or dose concentrations of TMR-001 or ribonuclease analogues should be investigated for this class of drugs as a rabies antiviral therapeutic.
- Subjects
RABIES virus; GOLDEN hamster; ANTIVIRAL agents; CENTRAL nervous system; INSULIN aspart; DRUG delivery devices
- Publication
Viruses (1999-4915), 2020, Vol 12, Issue 2, p177
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v12020177