Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2.

Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH.

Department of Medicine, Medical College of Georgia, Augusta 30912-2100, USA.

Valacyclovir is a prodrug of the antiviral agent acyclovir and it does not contain a peptide bond in its structure. We studied the interaction of valacyclovir with the peptide transporters in the human intestinal cell line Caco-2 and the rat kidney proximal tubular cell line SKPT which differentially express peptide transporters PEPT1 and PEPT2. The results of the studies done with these cell lines were confirmed with the cloned peptide transporters human PEPT1 and rat PEPT2, expressed heterologously in HeLa cells. The activity of the peptide transporters was assessed by measuring the uptake of radiolabeled glycylsarcosine in the presence of a H+ gradient. Valacyclovir inhibited the uptake of glycylsarcosine with an inhibition constant (Ki) of 0.49 +/- 0.04 mM in Caco-2 cells and 0.17 +/- 0.01 mM in SKPT cells. In both cell types, the inhibition was competitive. Acyclovir, in contrast to valacyclovir, did not interact with the peptide transporters. Similar results were obtained with heterologously expressed human PEPT1 and rat PEPT2. Valacyclovir inhibited the hPEPT1-mediated glycylsarcosine transport competitively with a Ki value of 0.74 +/- 0.14 mM. The rPEPT2-mediated transport of glycylsarcosine was also inhibited by valacyclovir competitively and the Ki value for the process was 0.39 +/- 0.03 mM. Acyclovir did not interact with either of these cloned peptide transporters. We conclude that valacyclovir is a substrate for the peptide transporters PEPT1 and PEPT2 and that a peptide bond is not a prerequisite for recognition as a substrate by the peptide transporters.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9610386&dopt=Abstract acyclovir Zovirax




J Microbiol Immunol Infect. 1997 Feb;30(1):51-4.
Screening for acyclovir-resistant herpes simplex virus isolates from clinical samples.

Mah IW, Kuo BI, Wei HY, Tsai CH, Liu WT.

Department of Laboratory Medicine, Veterans General Hospital, Taipei.

The ID90 or ID50 values of acyclovir for the herpes simplex virus strains isolated in VGH-Taipei were determined by plaque reduction method. Twenty HSV isolates of 1980's (1980-1985) and thirty of 1990's (1990-1995) were subjected to plaque reduction assay for susceptibility test to acyclovir. There were fifteen HSV isolates of 1990's whose ID90 were higher than those of 1980's, indicating a trend of more acyclovir resistant isolates in 1990's.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10592810&dopt=Abstract acyclovir Zovirax




Vopr Virusol. 1999 Nov-Dec;44(6):247-9.
[Isolation of acyclovir-resistant strains of herpes simplex virus from clinical material]

[Article in Russian]

L'vov ND, Andronova VL, Leont'eva NA, Galegov GA.

A total of 115 strains of herpes simplex virus were isolated from clinical material collected in patients with genital herpes. The majority (93%) of isolated strains were sensitive to acyclovir: ID50 varied from 0.15 to 0.80 microgram/ml acyclovir. Eleven (7%) strains from 4 patients were resistant to acyclovir: ID50 was 30-125 times higher in comparison with the reference HSV-1 strain L2.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10665057&dopt=Abstract acyclovir Zovirax




Antiviral Res. 1998 Jul;39(1):25-33.
Suppression of recurrent genital herpes simplex virus type 2 infection by Rhus javanica in guinea pigs.

Nakano M, Kurokawa M, Hozumi T, Saito A, Ida M, Morohashi M, Namba T, Kawana T, Shiraki K.

Department of Virology, Toyama Medical and Pharmaceutical University, Japan.

Rhus javanica has been shown to exhibit anti-herpes simplex virus (HSV) activity and potentiate the anti-HSV activity of acyclovir in vitro and in vivo. This extract was examined for its suppressive efficacy on recurrent genital infection in guinea pigs. Guinea pigs were primarily infected intravaginally with HSV type 2 (HSV-2). Prophylactic oral administration, at the dose corresponding to human use, of R. javanica significantly reduced the incidence, severity and/or frequency of spontaneous and severe skin lesions as compared with latently infected guinea pigs administered with water. This prophylactic efficacy was confirmed by the crossover administration, for more than 2 months, of R. javanica and water to the infected guinea pigs. Toxicity, such as weight loss, from R. javanica administration was not observed in the guinea pigs. When recurrent HSV-2 disease was induced by ultraviolet irradiation 3 months after primary infection, the prophylaxis with R. javanica was also significantly effective in reducing the severity of ultraviolet-induced skin lesions. Thus, prophylaxis of recurrent genital HSV-2 infection with R. javanica may preserve the efficacy of acyclovir by reducing both the use of acyclovir and the appearance of acyclovir-resistant viruses.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9754947&dopt=Abstract acyclovir Zovirax




Virology. 1997 Nov 10;238(1):53-63.
Acyclovir blocks cytokine gene expression in trigeminal ganglia latently infected with herpes simplex virus type 1.

Halford WP, Gebhardt BM, Carr DJ.

Department of Microbiology and Immunology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.

We have previously found that interleukin (IL)-2, IL-10, interferon (IFN)-gamma, RANTES, and tumor necrosis factor (TNF)-alpha mRNA transcription remain elevated in the trigeminal ganglia (TG) of herpes simplex virus type 1 (HSV-1) latently infected mice up to 120 days postinoculation (p.i.). To determine if this phenomenon was dependent on HSV-1 DNA replication after the establishment of latency (i.e., reactivation), cytokine gene expression was compared in TG of acyclovir-treated and untreated latently infected mice. Oral acyclovir treatment (begun 16 days p.i.) had no effect on serum levels of total anti-HSV-1 antibodies. However, there was a significant reduction in the titer of antibody specific for glycoprotein D and glycoprotein B but not glycoprotein H/L 120 days PI in the acyclovir-treated compared to vehicle-treated mice. These differences were not significant at earlier time points (i.e., days 34 and 60 p.i.). Consistent with these findings, acyclovir had no effect on cytokine gene expression in latently infected TG 35 and 60 days p.i. However, 120 days p.i., IFN-gamma and TNF-alpha mRNA were approaching baseline levels in TG of acyclovir-treated mice, but remained significantly elevated in untreated controls (i.e., IFN-gamma mRNA levels were sixfold higher in TG of untreated mice). Therefore, viral DNA replication appears to provide an antigenic stimulus for persistent cytokine gene expression in latently infected TG.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9375008&dopt=Abstract acyclovir Zovirax