Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro
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 neur...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/2/177 |
| _version_ | 1819139022371422208 |
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| author | Todd G. Smith Felix R. Jackson Clint N. Morgan William C. Carson Brock E. Martin Nadia Gallardo-Romero James A. Ellison Lauren Greenberg Thomas Hodge Luis Squiquera Jamie Sulley Victoria A. Olson Christina L. Hutson |
| author_facet | Todd G. Smith Felix R. Jackson Clint N. Morgan William C. Carson Brock E. Martin Nadia Gallardo-Romero James A. Ellison Lauren Greenberg Thomas Hodge Luis Squiquera Jamie Sulley Victoria A. Olson Christina L. Hutson |
| author_sort | Todd G. Smith |
| collection | DOAJ |
| description | 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 (<i>n</i> = 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. |
| first_indexed | 2024-12-22T11:16:03Z |
| format | Article |
| id | doaj.art-71fa94ae4d28456faa8722a4ab986a90 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-22T11:16:03Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-71fa94ae4d28456faa8722a4ab986a902022-12-21T18:28:00ZengMDPI AGViruses1999-49152020-02-0112217710.3390/v12020177v12020177Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In VitroTodd G. Smith0Felix R. Jackson1Clint N. Morgan2William C. Carson3Brock E. Martin4Nadia Gallardo-Romero5James A. Ellison6Lauren Greenberg7Thomas Hodge8Luis Squiquera9Jamie Sulley10Victoria A. Olson11Christina L. Hutson12Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USATamir Biotechnology, Inc. 12625 High Bluff Drive Suite 113, San Diego, CA 92130, USATamir Biotechnology, Inc. 12625 High Bluff Drive Suite 113, San Diego, CA 92130, USATamir Biotechnology, Inc. 12625 High Bluff Drive Suite 113, San Diego, CA 92130, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, USACurrently, 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 (<i>n</i> = 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.https://www.mdpi.com/1999-4915/12/2/177rabies viruslyssavirusantiviralranpirnase tmr-001onconasehamster |
| spellingShingle | Todd G. Smith Felix R. Jackson Clint N. Morgan William C. Carson Brock E. Martin Nadia Gallardo-Romero James A. Ellison Lauren Greenberg Thomas Hodge Luis Squiquera Jamie Sulley Victoria A. Olson Christina L. Hutson Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro Viruses rabies virus lyssavirus antiviral ranpirnase tmr-001 onconase hamster |
| title | Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro |
| title_full | Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro |
| title_fullStr | Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro |
| title_full_unstemmed | Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro |
| title_short | Antiviral Ranpirnase TMR-001 Inhibits Rabies Virus Release and Cell-to-Cell Infection In Vitro |
| title_sort | antiviral ranpirnase tmr 001 inhibits rabies virus release and cell to cell infection in vitro |
| topic | rabies virus lyssavirus antiviral ranpirnase tmr-001 onconase hamster |
| url | https://www.mdpi.com/1999-4915/12/2/177 |
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