title: A novel benzo-heterocyclic amine derivative N30 inhibits influenza virus replication by depression of Inosine-5'-Monophospate Dehydrogenase activity.
abstract: Influenza virus is still a huge threat to the world-wide public health. Host inosine-5'- monophosphate dehydrogenase (IMPDH) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. Herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative N30, which was designed to inhibit IMPDH.
  
  
  
  The results demonstrated that N30 inhibited the replication of H1N1, H3N2, influenza B viruses, including oseltamivir and amantadine resistant strains in vitro. Mechanistically, neuraminidase inhibition assay and hemagglutination inhibition assay suggested that N30 did not directly target the two envelope glycoproteins required for viral adsorption or release. Instead, the compound could depress the activity of IMPDH type II. Based on these findings, we further confirmed that N30 provided a strong inhibition on the replication of respiratory syncytial virus, coronavirus, enterovirus 71 and a diverse strains of coxsackie B virus.
  
  
  
  We identified the small molecule N30, as an inhibitor of IMPDH, might be a potential candidate to inhibit the replication of various viruses.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yan
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Dajun
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhuorong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. yuhuanlibj@126.com.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000588:Amines / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D017934:Coronavirus / Q000187:drug effects; D029821:Enterovirus A, Human / Q000187:drug effects; D029822:Enterovirus B, Human / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000502:physiology; D009981:Influenza B virus / Q000187:drug effects* / Q000502:physiology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000588:Amines; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007168:IMP Dehydrogenase
keywords: Benzo-heterocyclic amine derivative; IMPDH; Influenza A virus