Wolfgang Bender

Publications (2)22.46 Total impact

• Article: New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease.

  Gerald Kleymann, Rüdiger Fischer, Ulrich A K Betz, Martin Hendrix, Wolfgang Bender, Udo Schneider, Gabriele Handke, Peter Eckenberg, Guy Hewlett, Veniamin Pevzner, [......], Jörg Keldenich, Axel Jensen, Jörg Kolb, Ute Bach, Andreas Popp, Jutta Mäben, Isabelle Frappa, Dieter Haebich, Oswald Lockhoff, Helga Rübsamen-Waigmann
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  ABSTRACT: The vast majority of the world population is infected with at least one member of the human herpesvirus family. Herpes simplex virus (HSV) infections are the cause of cold sores and genital herpes as well as life-threatening or sight-impairing disease mainly in immunocompromized patients, pregnant women and newborns. Since the milestone development in the late 1970s of acyclovir (Zovirax), a nucleosidic inhibitor of the herpes DNA polymerase, no new non-nucleosidic anti-herpes drugs have been introduced. Here we report new inhibitors of the HSV helicase-primase with potent in vitro anti-herpes activity, a novel mechanism of action, a low resistance rate and superior efficacy against HSV in animal models. BAY 57-1293 (N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide), a well-tolerated member of this class of compounds, significantly reduces time to healing, prevents rebound of disease after cessation of treatment and, most importantly, reduces frequency and severity of recurrent disease. Thus, this class of drugs has significant potential for the treatment of HSV disease in humans, including those resistant to current medications.
  Nature Medicine 05/2002; 8(4):392-8. · 22.46 Impact Factor
• Article: Inhibition of murine cytomegalovirus and human cytomegalovirus by a novel non-nucleosidic compound in vivo

  Olaf Weber, Wolfgang Bender, Peter Eckenberg, Siegfried Goldmann, Michael Haerter, Sabine Hallenberger, Kerstin Henninger, Jürgen Reefschläger, Jörg Trappe, Astrid Witt-Laido, Helga Ruebsamen-Waigmann
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  ABSTRACT: 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 ≥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.
  Antiviral Research.