Acyclovir

ACV decreases viral DNA formation in infected cells without having an effect on non-infected cells. Viruses use the nucleotides supplied by host cells to replicate and produce new viruses. In this process, RNA thymine nucleosides are converted to monophosphate nucleosides by an enzyme found in the virus called viral thymidine kinase (TK). The monophosphate nucleoside is then converted to diphosphate and triphosphate nucleosides by the cells' own kinases. ACV functions in an almost identical fashion. ACV is a substrate of the viral replication process, which in uninfected cells, is barely converted. After it has been synthesized, ACV triphosphate is added to the viral DNA chain. However, it is structurally different from the deoxynucleotides of DNA. ACV triphosphate is missing the 3’-hydroxyl group of the sugar, thus further elongation of the DNA strand cannot occur. Viral DNA polymerase has a greater affinity for ACV triphosphate than it does for deoxyguanosine triphosphate (dGTP), the substrate of viral DNA polymerase, and therefore, it competes with dGTP for binding sites. This binding results in inhibition of the viral polymerase.

Fig. 1 The infected cell and activation of acyclovir. (Hassan Abed Z. 2025)

Acyclovir (ACV) is an antiviral drug with an intermediate solubility and low permeability profile. The poor permeability of ACV contributes to the drug's poor absorption and, therefore, low bioavailability. The administration of the drug to achieve ACV concentrations in the therapeutic range has to be frequent and, as a result, the administration of the drug more often increases the side effects. The improvement in the permeability of ACV is, therefore, crucial to its improved bioavailability, therapeutic success, and patient adherence.
To improve the permeability of ACV, Verma et al prepared polymeric micelles using a modified nanoprecipitation method to encapsulate ACV using acid-functionalized PJL-based amphiphilic copolymers mPEG-b-PJL-COOH and the corresponding homopolymer B-PJL-COOH. The in vitro permeation experiments demonstrated that the intestinal permeability of ACV, when delivered in micelles, was significantly increased, compared to free ACV and this was further supported by the in silico pharmacokinetic modeling prediction. A cytotoxicity assay displayed a concentration- and cell-dependent toxicity and validated that the concentrations used in the antiviral study were nontoxic. The results demonstrated that the ACV micelles are a promising nanocarrier for the enhanced stability, bioavailability, and aqueous solubility of ACV.

Fig. 2 Micelles containing polyjasmine lactone encapsulating acyclovir. (Verma J, et al. 2025)