Kidney Week

Abstract: SA-PO641

Activity of Brincidofovir (BCV) Against Murine Polyoma Virus (MuPyV) in a Mouse Infection Model

Session Information

• Pharmacology
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Naderer, Odin, Chimerix, Durham, North Carolina, United States

Odin Naderer,

• Colton, Heidi, Chimerix, Durham, North Carolina, United States

Heidi Colton,

• Jin, Ge, Pennsylvania State University, Hershey, Pennsylvania, United States

Ge Jin,

• Lauver, Matthew D., Pennsylvania State University, Hershey, Pennsylvania, United States

Matthew D. Lauver,

• Lukacher, Aron, Pennsylvania State University, Hershey, Pennsylvania, United States

Aron Lukacher,

Background

BK virus (BKV) is a ubiquitous polyomavirus which can result in up to 10% of kidney transplant recipients to develop BKV-associated nephropathy and organ loss. As no antivirals are available, the current treatment paradigm is reduction of immunosuppression which can risk organ rejection. An active antiviral capable of reducing BK viral burden while maintaining optimal immunosuppression could have a substantial impact on the survival of existing kidney grafts and avoid re-transplantation. BCV is a lipid conjugated nucleotide analog of cidofovir (CDV) with potent antiviral activity against BKV in vitro (EC₅₀= 0.02 uM) without CDV-associated nephrotoxicity. In this study, we assessed the in vivo antiviral activity of BCV against a murine polyomavirus (MuPyV) which infects the kidney in a mouse model.

Methods

Fifteen C57BL/6 mice (8–12 weeks old) were randomized 1:1:1 to placebo, BCV 20mg/kg or BCV 40mg/kg IP twice weekly. Treatment was given on Day -7, Day -3, Day 1, and Day 4. Mice were inoculated in hind footpads with 1.0 × 10⁶ PFU of MuPyV on Day 1. qPCR of kidney and spleen were performed at Day 5 (Termination).

Results

All mice tolerated all BCV IP doses to termination. BCV 20 mg/kg or higher delivered IP decreased viral load in the kidney by ~1 log.

Conclusion

BCV demonstrated antiviral activity in mice infected with MuPyV in this prophylaxis model. Evaluation of BCV activity in a post -infection treatment model of MuPyV is warranted to support BCV as a potential treatment for BKV.

Funding

• Commercial Support – Chimerix