4.5 Article

Ranpirnase (OKG-0301), a Novel Ribonuclease, Demonstrates Antiviral Activity against Adenovirus in the Ad5/NZW Rabbit Ocular Replication Model

期刊

PATHOGENS
卷 11, 期 12, 页码 -

出版社

MDPI
DOI: 10.3390/pathogens11121485

关键词

ranpirnase; RNase; antiviral; eye; adenovirus; EKC; animal model

资金

  1. Okogen, Pty Ltd.
  2. NIH Core Grant for Vision Research [EY08098]
  3. Eye & Ear Foundation of Pittsburgh
  4. Research to Prevent Blindness

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This study aimed to determine the antiviral activity of topical formulations of ranpirnase (OKG-0301) on adenoviral replication. The results showed that OKG-0301 exhibited strong antiviral activity and may be a potential candidate for the treatment of adenoviral eye infections.
Adenovirus ocular infections are common ocular viral infections seen worldwide, for which there is no approved antiviral therapy available. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA resulting in an inhibition of protein synthesis. The study goal was to determine the anti-adenoviral activity of topical formulations of ranpirnase (OKG-0301) on adenoviral replication in the Ad5/NZW rabbit ocular replication model. NZW rabbits were inoculated in both eyes with human adenovirus type 5 (HAdV5) after corneal scarification. A day later, topical therapy was initiated in both eyes with 0.03% OKG-0301, 0.003% OKG-0301, saline or 0.5% cidofovir. Eyes were cultured to determine HAdV5 eye titers over 2 weeks. OKG-0301 (0.03% and 0.003%) and 0.5% cidofovir decreased viral titers compared to saline. Furthermore, both OKG-0301 formulations and 0.5% cidofovir shortened the duration of the HAdV5 infection compared to saline. Both 0.03% OKG-0301 and 0.003% OKG-0301 demonstrated increased antiviral activity compared to saline in the Ad5/NZW rabbit ocular replication model. The antiviral activity of the OKG-0301 groups was similar to that of the positive antiviral control, 0.5% cidofovir. Ranpirnase (OKG-0301) may be a potential candidate for a topical antiviral for adenoviral eye infections. Further clinical development is warranted.

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