Adv Exp Med Biol. 2021;1322:1-30. doi: 10.1007/978-981-16-0267-2_1.
The discovery of the nucleoside analogue, acyclovir, represented a milestone in the management of infections caused by herpes simplex virus and varicella-zoster virus. Ganciclovir, another nucleoside analogue, was then used for the management of systemic and organ-specific human cytomegalovirus diseases. The pyrophosphate analogue, foscarnet, and the nucleotide analogue, cidofovir, have been approved subsequently and constitute the second-line antiviral drugs. However, the viral DNA polymerase is the ultimate target of all these antiviral agents with a possible emergence of cross-resistance between these drugs. Recently, letermovir that targets the viral terminase complex was approved for the prophylaxis of human cytomegalovirus infections in hematopoietic stem cell transplant recipients. Other viral targets such as the protein kinase and the helicase-primase complex are also evaluated for the development of novel potent inhibitors against herpesviruses.