Inhibitors of Viral DNA Polymerase

Abstract

Abstract Viral DNA polymerase offers an attractive target for the development of anti-viral agents. Many DNA viruses encode a DNA polymerase. Examples include adenoviruses (AdV) (Challberg and Kelly 1989), poxviruses such as vaccinia virus (Moss 1986), and herpes viruses such as herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), human cytomegalovirus (CMV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBY) (Roizman, and Batterson 1986). The DNA polymerase of these viruses is a key enzyme for their replication. Further, the viral DNA polymerases often differ enough from the host DNA polymerases to allow some degree of selective inhibition of the viral enzyme over the host DNA polymerases. In addition to the inherent differences between the viral and host DNA polymerases, specificity in inhibiting the viral DNA polymerase over the host enzymes can be achieved through the exploitation of other biochemical differences between infected and uninfected cells. Such differences could include membrane changes associated with the viral infection that allow anti-viral agents to penetrate infected cells more easily or metabolic changes that allow the selective activation of pro-drugs in infected cells.