Inhibition of Porcine Cytomegalovirus/Porcine Roseolovirus (PCMV/PRV) Replication with Antiviral Compounds.

The global organ shortage has driven significant interest in xenotransplantation, accelerated by advances in immunology and genetic engineering. However, infectious complications and immune responses remain incompletely understood. Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) is endemic in pigs and has been transmitted to xenotransplant recipients, where it may contribute to graft dysfunction. We evaluated FDA-approved and investigational antivirals against PCMV/PRV replication in vitro using plaque assays and quantitative PCR (qPCR) of the PCMV/PRV polymerase. The most efficacious agents by qPCR were DNA polymerase inhibitors brincidofovir (EC50 0.01 μM), cidofovir (EC50 1.65 μM), cyclopropavir (EC50 2.13 μM), and oxazolidinone amide derivatives (EC50 1-3 μM); hPMPA was also active (EC50 8.37 μM). Ganciclovir showed reduced activity compared to Human CMV (HCMV, EC50 18.07 μM), and foscarnet EC50 was 93.64 μM. FDA-approved antivirals acyclovir, maribavir, and letermovir were inactive or showed reduced activity compared to their anti-HCMV activity. The investigational drug pritelivir was also inactive. Two investigational HCMV inhibitors, MLS8554 and MLS8091, inhibited PCMV/PRV. Antiviral anticellular agents artesunate, artemisinin dimer 838, emetine, and digitoxin inhibited PCMV/PRV at concentrations comparable to HCMV inhibition. Emetine (EC50 0.03 μM) and digitoxin (EC50 0.010 μM) were the most potent. Artesunate was additive when combined with active PCMV/PRV inhibitors. This extensive investigation reveals a PCMV/PRV inhibition pattern similar to that of HHV-6. Although several compounds showed in vitro activity, their clinical utility must be weighed against toxicity at effective concentrations. Additional studies are needed to identify effective antivirals for PCMV/PRV and to optimize drug combination strategies.