Mechanisms of Resistance of Antiviral Drugs Active Against the Human Herpes Viruses

The antiviral drugs against the human herpesviruses provided pioneering insights, which have led to the development of the field of antiviral therapy. The first successful use of antiviral drugs to treat any life-threatening viral infection was vidarabine (adenine arabinoside) in 1977 [1]. This was followed by the development of acyclovir as the first specific antiviral drug which required a viral enzyme (thymidine kinase, TK) for activation to a nucleoside triphosphate, which inhibited the viral DNA polymerase and was a chain-terminator of viral DNA elongation [2, 3]. When tested against clinical viral isolates, acyclovir was most effective against those herpesviruses which established latency in neuronal tissue, (HSV-1, HSV-2, VZV) [4] with some activity against EBV, and very little against clinical isolates of CMV in a plaque reduction assay [4, 5]. With the possible exception of influenza A virus and amantadine, this marked the beginnings of antiviral therapy.