Acyclovir is one of the oldest antiviral drugs, having been in use for three decades now. It is an acyclic guanosine derivative and has activity mainly against herpes virus-1 (HSV-1), herpes virus-2 (HSV-2), and varicella zoster virus (VZV). It is only weakly active against Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6), and not used for these infections. It acts by inhibition of viral DNA synthesis. Before it can act, it has to be phosphorylated by virus-specific thymidine kinase. This step gives it a high therapeutic index, but is also a major mechanism of viral resistance.