- Vidarabine, also known as Adenine arabinoside or ara-A, is a synthetic purine nucleoside analog used primarily as an antiviral agent.
- It was one of the earliest antiviral drugs developed and was initially introduced in the 1970s for the treatment of herpes simplex virus (HSV) infections, particularly in cases involving encephalitis and keratitis.
- Structurally, vidarabine is an analog of adenosine, where the ribose sugar is replaced with arabinose—a pentose sugar that differs from ribose in the stereochemistry of its 2’ hydroxyl group. This subtle change allows vidarabine to mimic adenosine in viral DNA synthesis while ultimately disrupting it.
- Vidarabine’s mechanism of action is centered around its conversion inside cells to the active triphosphate form, ara-ATP. This molecule competes with deoxyadenosine triphosphate (dATP) during viral DNA replication. When incorporated into viral DNA by DNA polymerase, ara-ATP results in premature chain termination, effectively inhibiting viral DNA synthesis. This mode of action makes it particularly effective against DNA viruses such as HSV-1, HSV-2, and varicella-zoster virus (VZV). Vidarabine also shows some activity against poxviruses, cytomegalovirus (CMV), and hepatitis B virus, although it has largely been supplanted in these cases by newer, more effective drugs.
- Clinically, vidarabine has been used in both topical and intravenous formulations. Topically, it has been employed in treating herpetic keratitis, an HSV-related eye infection. Intravenous administration has been used for severe HSV infections, including neonatal herpes and herpes encephalitis. However, its use is limited by poor oral bioavailability and a relatively narrow therapeutic window. Furthermore, resistance can develop through mutations in viral DNA polymerase, and toxicity—particularly hematologic and gastrointestinal side effects—can be dose-limiting.
- Over time, vidarabine has been largely replaced by safer and more effective antiviral agents, particularly acyclovir and its derivatives. Acyclovir has better pharmacokinetics, lower toxicity, and greater selectivity for viral polymerase, making it the preferred treatment for most HSV and VZV infections today. Nevertheless, vidarabine played a crucial role in the early development of antiviral chemotherapy and set the stage for the rational design of nucleoside analogs targeting viral replication.
