The helicase-primase inhibitor BAY 57-1293 reduces the Alzheimer's disease-related molecules induced by herpes simplex virus type 1.

Abstract

Herpes simplex virus type 1 (HSV1) infection of cultured cells causes the formation of β-amyloid (Aβ) and abnormal tau (P-tau). These molecules comprise the main components of the abnormal protein deposits, amyloid plaques and neurofibrillary tangles, respectively, in Alzheimer's disease (AD) brains, and they have been implicated in disease development. The formation of P-tau, but not of Aβ, depends on viral DNA replication, but nonetheless, three antiviral agents that inhibit HSV1 DNA replication, including acyclovir (ACV), were found to reduce greatly the level of Aβ as well as P-tau, the former probably through prevention of viral spread. Previous studies showed that HSV1 DNA is present and is active in the brain of many elderly people, including AD patients, and that in combination with the type 4 allele of the apolipoprotein E gene, it is likely to play a role in the disease, perhaps via Aβ and P-tau production. With the aim of finding the most suitable antiviral for inhibiting Aβ and P-tau formation as well as HSV1 DNA replication, for future use in a clinical trial for treating AD, we compared the efficacy of ACV with that of another antiviral, BAY 57-1293, which acts by a different mechanism from ACV. We found that BAY 57-1293 is more efficient than ACV not only in inhibiting HSV1 replication, confirming previous studies, but also in decreasing Aβ and P-tau formation. Also, the cell clusters that are formed during infection are reduced in size much more efficiently by BAY 57-1293 than by ACV. These data suggest that BAY 57-1293 would be a more effective agent than ACV for treating AD.

• Authors: M A Wozniak, A L Frost, R F Itzhaki
• Journal: Antiviral research (Antiviral Res) Vol. 99 Issue 3 Pg. 401-4 (Sep 2013) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 23867133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Antiviral Agents
• Enzyme Inhibitors
• Pyridines
• Sulfonamides
• Thiazoles
• Viral Proteins
• tau Proteins
• pritelivir
• DNA Primase
• helicase-primase, Human herpesvirus 1
• DNA Helicases
• Acyclovir

Topics

• Acyclovir (pharmacology)
• Alzheimer Disease (drug therapy, metabolism, virology)
• Amyloid beta-Peptides (genetics, metabolism)
• Antiviral Agents (pharmacology)
• DNA Helicases (antagonists & inhibitors)
• DNA Primase (antagonists & inhibitors)
• Down-Regulation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Herpes Simplex (drug therapy, metabolism, virology)
• Herpesvirus 1, Human (drug effects, enzymology, genetics, metabolism)
• Humans
• Pyridines (pharmacology)
• Sulfonamides
• Thiazoles (pharmacology)
• Viral Proteins (antagonists & inhibitors)
• Virus Replication (drug effects)
• tau Proteins (genetics, metabolism)