Acyclovir is a potent oral antiviral drug. Acyclovir has anti-herpetic activity with IC50 values of 0.85 μM and 0.86 μM for HSV-1 and HSV-2, respectively. Acyclovir induces cell cycle disruption and apoptosis[1] [2].
In the plaque reduction assay (PRA) of Vero cells, Acyclovir (20μM; 3d) treatment showed 100% plaque inhibition[1]. Acyclovir (10-100μM; 24-72h) blocks DNA synthesis, thereby arresting the cell cycle at G2/M and S phases and increasing the G1 hypodiploid peak in a dose-dependent manner. Acyclovir (10-100μM; 24-72h) induces apoptosis through activation of caspase-3 and the presence of nuclear DNA fragmentation[2].
Treatment of infected mice with Acyclovir (20mg/kg; po; three times daily; 10d) inhibited the development of skin lesions and led to a dissociation between the DTH response and antibody production [3]. In the Acyclovir-induced nephrotoxicity model, after mice were given Acyclovir (150, 600 mg/kg; ip; 9d), serum creatinine and urea nitrogen levels increased, histopathological changes occurred in the kidneys of mice, and the expression levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 were reduced[4].
References:
[1]. Musarra-Pizzo M, Pennisi R, Ben-Amor I, et al. In vitro anti-HSV-1 activity of polyphenol-rich extracts and pure polyphenol compounds derived from pistachios kernels (Pistacia vera L.)[J]. Plants, 2020, 9(2): 267.
[2].Suzuki M, Okuda T, Shiraki K. Synergistic antiviral activity of Acyclovir and vidarabine against herpes simplex virus types 1 and 2 and varicella-zoster virus[J]. Antiviral research, 2006, 72(2): 157-161.
[3]. Benedetti S, Catalani S, Palma F, et al. Acyclovir induces cell cycle perturbation and apoptosis in Jurkat leukemia cells, and enhances chemotherapeutic drug cytotoxicity[J]. Life sciences, 2018, 215: 80-85.
[4].Lu H, Han Y J, Xu J D, et al. Proteomic characterization of acyclovir-induced nephrotoxicity in a mouse model[J]. PLoS One, 2014, 9(7): e103185.