Fifty Years in Search of Selective Antiviral Drugs

Fifty years of research (1968-2018) toward the identification of selective antiviral drugs have been primarily focused on antiviral compounds active against DNA viruses (HSV, VZV, CMV, HBV) and retroviruses (HIV). For the treatment of HSV infections the aminoacyl esters of acyclovir were designed, and valacyclovir became the successor of acyclovir in the treatment of HSV and VZV infections. BVDU (brivudin) still stands out as the most potent among the marketed compounds for the treatment of VZV infections (i.e., herpes zoster). In the treatment of HIV infections 10 tenofovir-based drug combinations have been marketed, and tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have also proved effective in the treatment of HBV infections. As a spin-off of our anti-HIV research, a CXCR4 antagonist AMD-3100 was found to be therapeutically useful as a stem cell mobilizer, and has since 10 years been approved for the treatment of some hematological malignancies.