Abstract
Omeprazole was shown to improve the anti-cancer effects of the nucleoside analogue 5-fluorouracil. Here, we combined omeprazole with the antiviral nucleoside analogues ribavirin and acyclovir. Omeprazole did not affect the antiviral effects of ribavirin in non-toxic concentrations up to 80 μg/mL but increased the acyclovir-mediated effects on herpes simplex virus 1 and 2 (HSV-1 and -2) replication in a dose-dependent manner. Omeprazole alone reduced HSV-1 and -2 titers [but not HSV-induced formation of cytopathogenic effects (CPE)] at concentrations ≥40 μg/mL. However, it exerted substantially stronger effects on acyclovir activity and also increased acyclovir activity at lower concentrations that did not directly interfere with HSV replication. Omeprazole 80 μg/mL caused a 10.8-fold (Vero cells) and 47.7-fold (HaCaT cells) decrease of the acyclovir concentrations that reduced HSV-1-induced CPE formation by 50% (IC50). In HSV-2-infected cells, omeprazole 80 μg/mL reduced the acyclovir IC50 by 7.3- (Vero cells) and 12.9-fold (HaCaT cells). In HaCaT cells, omeprazole 80 μg/mL reduced the HSV-1 titer in the presence of acyclovir 1 μg/mL by 1.6 × 105-fold and the HSV-2 titer in the presence of acyclovir 2 μg/mL by 9.2 × 103-fold. 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 a 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.
Highlights
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, 2004; Ikemura et al, 2017)
Omeprazole 80 μg/mL did not alter the effects of ribavirin on Cytopathogenic Effect (CPE) formation in West Nile virus (WNV)-infected Vero cells or H1N1-infected MDCK cells (Figure 1A and Supplementary Table S1)
herpes simplex virus 1 (HSV-1)- and HSV-2-induced CPE formation were investigated in Vero and HaCaT cells
Summary
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, 2004; Ikemura et al, 2017). Proton pump inhibitors are the most frequently prescribed drugs for the treatment and prophylaxis of gastroesophageal reflux as well as of gastric and duodenal ulcers that are associated with hyper-acidic states. Since they are known to be well-tolerated, they were suggested as repositioning candidates for the Omeprazole Increases Acyclovir Efficacy use as part of anti-cancer therapies (Luciani et al, 2004; Ikemura et al, 2017). Our findings show that omeprazole (and other proton pump inhibitors) increase the antiviral activity of acyclovir but not that of ribavirin
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
