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 inhibitors of the human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) in vitro. We have now investigated the antiviral activity of these compounds in MCMV-infected NOD/LtSz-scid/j mice that lack functional T, B and, in contrast to C.B-17/Icr scid/scid mice, natural killer cells, and represent a novel model for cytomegalovirus infection in immunocompromised hosts. BAY 38-4766 (3-hydroxy-2,2-dimethyl-N-[4(([5-(dimethylamino)-1-naphthyl]sulfonyl)amino)- phenyl]propanamide) was identified as the most potent representative of this class of antiviral compounds. Per os administration of BAY 38-4766 at dosages > or = 10 mg/kg body weight led to antiviral effects that were comparable to ganciclovir 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (Cymevene) as measured by survival and levels of viral DNA in organs of infected mice. In order to assess the anti-HCMV activity of BAY 38-4766 in vivo, we used a model, in which HCMV-infected human 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.
Weber
O
O
Department of Antiinfective Research, BAYER AG Pharmaceutical Research Centre, 42096 Wuppertal, Germany. olaf.weber.b@bayer.com
Bender
W
W
Eckenberg
P
P
Goldmann
S
S
Haerter
M
M
Hallenberger
S
S
Henninger
K
K
Reefschläger
J
J
Trappe
J
J
Witt-Laido
A
A
Ruebsamen-Waigmann
H
H
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000254:growth & development; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000821:virology; D008099:Liver / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009282:Naphthalenesulfonates / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D011355:Prodrugs / Q000494:pharmacology; D012469:Salivary Glands / Q000821:virology
C434759:3-(2-aminoacetato)-2,2-dimethyl-N-(4(((5-(dimethylamino)-1-naphthyl)sulfonyl)amino)-phenyl)propanamide; C434758:3-hydroxy-2,2-dimethyl-N-(4(((5-(dimethylamino)-1-naphthyl)sulfonyl)amino)phenyl)propanamide; D000998:Antiviral Agents; D004279:DNA, Viral; D009282:Naphthalenesulfonates; D011355:Prodrugs