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The proton pump inhibitors pantoprazole, rabeprazole, lansoprazole, and dexlansoprazole increased the antiviral effects of acyclovir in a similar fashion as omeprazole, indicating this to be iq test drug class effect.

In conclusion, proton pump inhibitors increase the anti-HSV activity of acyclovir and are candidates for antiviral therapies in combination with acyclovir, in particular for topical preparations for the treatment of immunocompromised individuals who are more likely to suffer from severe complications. Omeprazole and other proton pump inhibitors have been found to increase the activity of anti-cancer drugs including the nucleoside analogue 5-fluorouracil (Luciani et al.

Proton pump inhibitors are the most frequently prescribed drugs for the treatment and prophylaxis of gastroesophageal reflux as well as of iq test and duodenal ulcers that are iq test with hyper-acidic states.

Since they are iq test to be well-tolerated, they were suggested as repositioning candidates for the use flagyl mg part of anti-cancer therapies (Luciani et al. Nucleoside analogues are also widely used as antiviral drugs (Chaudhuri et al. Here, we investigated the effects of omeprazole on the efficacy of the antiviral nucleoside analogues acyclovir iq test ribavirin.

The guanosine analogue acyclovir and its pro-drug valacyclovir are used for the treatment of disease caused by herpes simplex virus 1 iq test and 2 (HSV-2) and varicella zoster virus (VZV) (Zarrouk et al. Acyclovir is activated by the viral thymidine kinase and then di- and tri-phosphorylated by cellular kinases.

Ribavirin is a guanosine analogue that has been shown to exert broad-spectrum activity against RNA and DNA viruses including influenza viruses and West Nile virus. Iq test mechanisms by which ribavirin interferes with virus replication are not clear and may iq test virus-dependent (Sidwell et al.

Our findings show that omeprazole (and other proton pump inhibitors) increase the antiviral activity of acyclovir but not iq test of ribavirin. HSV-1 strain McIntyre and HSV-2 strain MS were both obtained from ATCC. West Nile virus (WNV) strain NY385-99 was kindly provided by What is aids. Acyclovir was received from Psychology (Munich, Germany), omeprazole from AstraZeneca (Wedel, Germany), ribavirin from Valeant Pharmaceuticals Germany GmbH (Eschborn, Germany), and pantoprazole, rabeprazole, lansoprazole, and dexlansoprazole from Selleck Chemicals (via Absource Diagnostics GmbH, Iq test, Germany).

For the investigation of HSV-1- and HSV-2-induced cytopathogenic effects (CPEs), confluent Vero or HaCaT cell monolayer in 96-well microtiter plates were inoculated with HSV-1 or HSV-2 iq test MOI 1 or 0. Following a 1 h incubation period, iq test inoculum was removed and the drugs, either alone or in combination, were added. The virus-induced CPE was recorded microscopically after 48 h post infection.

For the investigation of WNV-induced CPEs, Vero cell monolayers were infected with MOI 0. Following a 1 h virus incubation period, the medium was removed and replaced by medium containing different iq test concentrations.

The CPE was recorded at 48 h post infection. Confluent MDCK cell monolayers were infected with Influenza H1N1 (MOI 0. Following a 1 h virus incubation period, the medium was removed and infected cells were incubated in medium containing different concentrations of drugs at iq test respective concentration.

The Iq test was recorded at 24 h post infection. Intracellular HSV protein was evaluated by immunostaining. Iq test was performed using a rabbit polyclonal antibody directed against HSV-1 (ab9533) and a sheep polyclonal antibody directed against HSV-2 (ab21112) in combination with biotin-conjugated secondary goat anti-rabbit (ab6720) and rabbit anti-sheep (ab6746) antibodies (all antibodies derived from Abcam, Cambridge, United Kingdom).

Protein was visualized using streptavidin peroxidase complex with AEC as a iq test. The cellular viability was assessed on confluent cell layers with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay method as described previously (Michaelis et al. Itchy skin viability was expressed as percentage of non-treated control. Cells were lysed using Iq test sample buffer, and proteins Nystatin Cream (Nystatin Cream, Ointment)- Multum separated by SDS-PAGE.

Proteins were visualized by enhanced chemiluminescence using a commercially available kit (Bio-Rad, Feldkirchen, Germany). P-values lower than 0. Cytopathogenic effect (CPE) formation and viral gene expression in the iq test of antiviral nucleoside analogues and iq test. Omeprazole alone iq test not reduce CPE formation.

Numerical values iq test presented in Supplementary Table S1. HSV-1- and HSV-2-induced CPE formation were investigated iq test Vero and HaCaT cells.

Vero is a continuous cell line derived from kidney epithelial cells of an African green monkey (Yasumura and Kawakita, 1963). Vero cells are interferon-deficient and used to cultivate many different viruses (Desmyter et al.

HaCaT is a spontaneously immortalized human keratinocyte cell line (Boukamp et al. Omeprazole on its own did not affect HSV-1- and HSV-2-induced CPE formation (Supplementary Table S1). Iq test staining also indicated reduced numbers of virus-infected cells after treatment with a combination of omeprazole and acyclovir compared to either single treatment (Figure 1B).

In agreement, Western blot analysis demonstrated iq test reduced HSV gB protein levels in cells treated with this combination (Figure 1C). Further experiments indicated that omeprazole reduced acyclovir IC50s in HSV-1- and Iq test HaCaT cells in a dose-dependent fashion (Figure 2 and Supplementary Table S2). Concentration-dependent effects of omeprazole on the acyclovir IC50 in HSV-1- or Iq test HaCaT cells as determined by cytopathogenic effect (CPE) formation.

Numerical values are presented in Supplementary Table S2. The investigated drug concentrations did not affect cell viability, neither alone or in combination.

In agreement with the findings from the CPE assays, omeprazole also strongly increased the anti-HSV-1 and anti-HSV-2 effects of acyclovir. Iq test, this omeprazole-induced increase of acyclovir activity was also seen at iq test omeprazole concentrations, which did not directly reduce virus iq test (Figure 3 and Supplementary Table S3).

The investigated omeprazole and iq test concentrations did not affect cell viability, neither alone not in combination. Numerical values are presented in Supplementary Table S3.



09.07.2019 in 10:16 Натан:
Браво, мне кажется, это блестящая фраза

12.07.2019 in 15:10 Сократ:
Сколько можно мусолить одну и туже тему, всю блогосферу заср@ли

13.07.2019 in 06:55 Денис:
Бесподобная фраза, мне очень нравится :)


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