title: Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.
abstract: Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9μM but was cytotoxic at concentrations only twofold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238-265μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3μM, significantly below its 50% cytotoxic concentration of 216μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to 1h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Zohaib
authors.initials: Z
authors.lastname: Alam
authors.affiliation: Medical Science Department, College of Nursing, University of Babylon, Babylon, Iraq.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Al-Mahdi
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: McKee
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Parris
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Hardik I
authors.initials: HI
authors.lastname: Parikh
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Glen E
authors.initials: GE
authors.lastname: Kellogg
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Kuchta
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA. Electronic address: mmcvoy@vcu.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McVoy
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology* / Q000633:toxicity; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D004279:DNA, Viral / Q000235:genetics; D004642:Emodin / Q000494:pharmacology / Q000633:toxicity; D015774:Ganciclovir / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors; D013451:Sulfonic Acids / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: C532474:1-amino-4-(2,4,6-trimethylanilino)anthraquinone-2-sulfonate; D000880:Anthraquinones; D000998:Antiviral Agents; D004279:DNA, Viral; D017874:Immediate-Early Proteins; D013451:Sulfonic Acids; C095110:UL98 protein, cytomegalovirus; C042834:9,10-anthraquinone; D004642:Emodin; D015774:Ganciclovir; C494012:alizarin violet; C529581:Acid Blue 40
keywords: Alkaline nuclease; Anthraquinone; Antivirals; Atanyl blue PRL; Cytomegalovirus