Ranpirnase acts on the infected host cell rather than on a viral protein. It preferentially enters infected cells to shut down viral replication and induce apoptosis, and its mechanism is virus- and strain-agnostic.
The result is broad-spectrum activity independent of viral strain, and a high barrier to resistance: there is no viral target to mutate away from.
Ranpirnase enters cells via endocytosis and works through four linked mechanisms.
It cleaves the double-stranded RNA produced by the virus, shutting down viral replication.
The fragmented dsRNA activates protein kinase R, which assists in fighting the infection.
By degrading tRNA while leaving rRNA and mRNA intact, viral proteins cannot be translated.
It targets miRNAs for destruction, activating ATF3, which leads to the death of the infected cell.
Has demonstrated therapeutic and prophylactic activity in preclinical models. May have potential for use during a suspected outbreak or following uncertain exposure.
Activity does not depend on binding the virus directly or on expression of a distinct viral protein, so it is expected to be independent of strain differences.
Prior clinical experience has not identified neutralising antibodies as a limitation to repeat dosing.
Its short systemic half-life limits accumulation, supported by substantial prior clinical exposure.
Intravenous for rapid exposure, plus topical solution, ointment and cream forms where systemic exposure is not needed.
Drug substance is extremely stable at −30 °C. Topical formulations exceed 24 months at 25 °C; intravenous formulations exceed 24 months at 5 °C.
Ranpirnase has been dosed in more than 1,000 patients to date by intravenous, topical ophthalmic and dermal delivery, providing extensive, well-characterized clinical safety experience.
Viruses tested
Highly potent — selectivity indices around or above 100
Moderately potent — selectivity indices above 10
Independent laboratories, including USAMRIID and the CDC
| Family | Virus | Cell line |
|---|---|---|
| Highly potent — selectivity indices around or above 100 | ||
| Filo | Ebola | Vero E6 |
| Orthomyxo | Influenza | NHBE |
| Flavi | Dengue | Vero |
| Flavi | Yellow fever | Vero |
| Toga | VEE | Astrocytes (primary) |
| Corona | MERS | NHBE |
| Retro | HIV | U937 |
| Polyoma | HPV | A431 |
| Picorna | Rhinovirus | NHBE |
| Parvo | Parvovirus | A72 |
| Paramyxo | RSV | NHBE |
| Herpes | HHV-6B | HSB2 / MOLT3 |
| Herpes | HCMV | HFF |
| Adeno | Adenovirus | NHBE |
| Rhabdo | Rabies | MNA, EF, BHK |
| Moderately potent — selectivity indices above 10 | ||
| Pox | Cowpox | Vero 76 |
| Toga | Chikungunya | U2OS |
| Bunya | Rift Valley fever | Vero 76 |
| Arena | Tacaribe | Vero 76 |
| Corona | SARS | Vero 76 |
| Herpes | HSV-1 | HFF |
| Paramyxo | Measles | Vero 76 |
| Flavi | HCV | Huh 7.5 |
