title: Mood stabilizers inhibit cytomegalovirus infection.
abstract: Cytomegalovirus (CMV) infection can generate debilitating disease in immunocompromised individuals and neonates. It is also the most common infectious cause of congenital birth defects in infected fetuses. Available anti-CMV drugs are partially effective but are limited by some toxicity, potential viral resistance, and are not recommended for fetal exposure. Valproate, valpromide, and valnoctamide have been used for many years to treat epilepsy and mood disorders. We report for the first time that, in contrast to the virus-enhancing actions of valproate, structurally related valpromide and valnoctamide evoke a substantial and specific inhibition of mouse and human CMV in vitro. In vivo, both drugs safely attenuate mouse CMV, improving survival, body weight, and developmental maturation of infected newborns. The compounds appear to act by a novel mechanism that interferes with CMV attachment to the cell. Our work provides a novel potential direction for CMV therapeutics through repositioning of agents already approved for use in psychiatric disorders.
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, 06510 New Haven, CT, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale Women and Children's Center for Blood Disorders and Preeclampsia Advancement, 333 Cedar Street, 06510 New Haven, CT, USA; School of Medicine and Surgery, Ph.D. Program in Neuroscience, University of Milan-Bicocca, via Cadore 48, 20900 Monza, Italy; Department of Obstetrics and Gynecology, Foundation MBBM, University of Milan-Bicocca, via Pergolesi 33, 20900 Monza, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ornaghi
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, 06510 New Haven, CT, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Davis
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, 06510 New Haven, CT, USA.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Gorres
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, 06510 New Haven, CT, USA.
authors.forename: George
authors.initials: G
authors.lastname: Miller
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale Women and Children's Center for Blood Disorders and Preeclampsia Advancement, 333 Cedar Street, 06510 New Haven, CT, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Paidas
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, 06510 New Haven, CT, USA. Electronic address: anthony.vandenpol@yale.edu.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: van den Pol
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000401:mortality / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018146:Muromegalovirus / Q000187:drug effects / Q000502:physiology; D014149:Tranquilizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000577:Amides; D014149:Tranquilizing Agents; C045179:valnoctamide; D014635:Valproic Acid; C004651:dipropylacetamide
keywords: Cytomegalovirus; Development; Mood stabilizers; Perinatal infection