Inhibition of murine cytomegalovirus and human cytomegalovirus by a novel non-nucleosidic compound in vivo

Novel non-nucleosidic compounds have recently been identified as potent inh ibitors of the human cytomegalovirus (HCMV) and murine cytomegalovirus (MCM V) in vitro. We have now investigated the antiviral activity of these compo unds in MCMV-infected NOD/LtSz-scid/j mice that lack functional T, B and, i n contrast to C.B-17/Icr scid/scid mice, natural killer cells, and represen t a novel model for cytomegalovirus infection in immunocompromised hosts. B AY 38-4766 (3-hydroxy-2,2-dimethyl-N-[4({[5-(dimethylamino)-1-naphthyl]sulf onyl}amino)-phenyl]propan-amide) amide) was identified as the most potent r epresentative of this class of antiviral compounds. Per os administration o f BAY 38-4766 at dosages greater than or equal to 10 mg/kg body weight led to antiviral effects that were comparable to ganciclovir 9-(1,3-dihydroxy-2 -propoxymethyl)-guanine (Cymevene (R)) as measured by survival and levels o f viral DNA in organs of infected mice. In order to assess the anti-HCMV ac tivity of BAY 38-4766 in vivo, we used a model, in which HCMV-infected huma n cells were entrapped in hollow fibers and subsequently transplanted into immunodeficient mice. Using this model, we demonstrated antiviral activity of BAY 38-4766 similar to that of ganciclovir. We conclude that BAY 38-4766 shows potential as an anti-HCMV drug. (C) 2001 Elsevier Science B.V. All r ights reserved.