Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses.

Journal Article (Journal Article)

The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2). varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system.

Full Text

Duke Authors

Cited Authors

  • Lillie, JW; Smee, DF; Huffman, JH; Hansen, LJ; Sidwell, RW; Kaddurah-Daouk, R

Published Date

  • April 1, 1994

Published In

Volume / Issue

  • 23 / 3-4

Start / End Page

  • 203 - 218

PubMed ID

  • 8042860

International Standard Serial Number (ISSN)

  • 0166-3542

Digital Object Identifier (DOI)

  • 10.1016/0166-3542(94)90018-3


  • eng

Conference Location

  • Netherlands