Abstract: PO2055
RBT-9 Antiviral Activity Against BK Virus
Session Information
- Transplantation: Evaluating Kidney Graft Injury - Pathways and Biomarkers
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1901 Transplantation: Basic
Authors
- Ruiz, Stacey, Renibus Therapeutics, Inc., Southlake, Texas, United States
- James, Scott, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Hartline, Caroll, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Singh, Bhupinder, University of California Irvine, Irvine, California, United States
Background
BK virus, a member of the polyomavirus family, is a significant risk factor for nephropathy and subsequent allograft loss in patients undergoing kidney transplantation. There are currently no approved treatments for BK virus-induced nephropathy. RBT-9, a novel formulation of stannous protoporphyrin (SnPP), exhibits broad antiviral activity against enveloped and nonenveloped viruses in vitro. It is also known to be protective against acute kidney injury (AKI) in animals when given prior to insult. Given the dual antiviral and kidney protective effects of RBT-9, the effect of RBT-9 against BK viral infection was investigated in vitro, as standard in vivo models that mimic BK virus complications are not currently available.
Methods
Two conditions were investigated: 1) standard qPCR-based antiviral assay – treatment with RBT-9 at the time of infection and 2) viral neutralization – pre-incubation of RBT-9 with BK virus for 1 hour prior to infection. RBT-9 was tested at concentrations up to 100 µM. Human foreskin fibroblast (HFF) cells were used as the host cell. Viral activity was assessed by real time qPCR and cellular viability was determined by CellTiter-Glo.
Results
RBT-9 exhibited moderate antiviral activity against BK virus under both treatment conditions. The 50% effective concentration (EC50) averaged 5.5 µM in 2 independently run standard qPCR assays and 5.4 µM in the neutralization assay. The EC50 of RBT-9 in these assays is 11 times lower than the highest dose of RBT-9 tested in Phase 1 studies and considered to be well tolerated. The 50% cytotoxic concentration (CC50) in the in vitro studies averaged 89.2 µM, indicating RBT-9 did not adversely affect host cell viability at concentrations 16.5 times higher than its effective concentration.
Conclusion
Given the antiviral activity of RBT-9 against BK virus in vitro and the safety profile of RBT-9 in Phase 1 human studies, a clinical study assessing the efficacy of RBT-9 is warranted in patients who are at risk of developing BK virus-induced nephropathy.
Funding
- Other NIH Support –