The non-nucleoside antiviral, BAY 38-4766, protects against cytomegalovirus (CMV) disease and mortality in immunocompromised guinea pigs

Mark R. Schleiss, David I. Bernstein, Michael A. McVoy, Greg Stroup, Fernando Bravo, Blaine Creasy, Alistair McGregor, Kristin Henninger, Sabine Hallenberger

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


New antiviral drugs are needed for the treatment of cytomegalovirus (CMV) infections, particularly in immunocompromised patients. These studies evaluated the in vitro and in vivo activity of the non-nucleosidic CMV inhibitor, BAY 38-4766, against guinea pig cytomegalovirus (GPCMV). Plaque reduction assays indicated that BAY 38-4766 was active against GPCMV, with an IC 50 of 0.5 μM. Yield reduction assays demonstrated an ED 90 and ED 99 of 0.4 and 0.6 μM, respectively, of BAY 38-4766 against GPCMV. Guinea pigs tolerated oral administration of 50 mg/kg/day of BAY 38-4766 without evidence of biochemical or hematologic toxicity. Plasma concentrations of BAY 38-4766 were high following oral dosing, with a mean peak level at 1-h post-dose of 26.7 mg/ml (n = 6; range, 17.8-35.4). Treatment with BAY 38-4766 reduced both viremia and DNAemia, as determined by a real-time PCR assay, following GPCMV infection of cyclophosphamide-immunosuppressed strain 2 guinea pigs (p < 0.05, Mann-Whitney test). BAY 38-4766 also reduced mortality following lethal GPCMV challenge in immunosuppressed Hartley guinea pigs, from 83% (20/24) in placebo-treated guinea pigs, to 17% (4/24) in BAY 38-4766-treated animals (p < 0.0001, Fisher's exact test). Mortality differences were accompanied by reduction in DNAemia in Hartley guinea pigs. Based upon its favorable safety, pharmacokinetic, and therapeutic profiles, BAY 38-4766 warrants further investigation in the GPCMV model.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalAntiviral Research
Issue number1
StatePublished - Jan 2005

Bibliographical note

Funding Information:
The excellent technical assistance of Amber-Renee Hickson, Kelly Pogorzelski, and Edward Tillitz is acknowledged. We also thank Rhonda Cardin for a critical review of the manuscript. This work was supported by National Institute of Health AI-65289 and HD38416-01, and by March of Dimes Basic Research Grants 6-FY98/99-0416 and FY01-22.


  • Antiviral therapy
  • BAY 38-4766
  • CMV infection
  • Cytomegalovirus
  • Guinea pig
  • Immunocompromised animal model
  • Placenta
  • Real-time PCR


Dive into the research topics of 'The non-nucleoside antiviral, BAY 38-4766, protects against cytomegalovirus (CMV) disease and mortality in immunocompromised guinea pigs'. Together they form a unique fingerprint.

Cite this