title: 6SLN-lipo PGA specifically catches (coats) human influenza virus and synergizes neuraminidase-targeting drugs for human influenza therapeutic potential.
abstract: OBJECTIVE
  The purpose of this study was to develop a new compound to overcome influenza epidemics and pandemics as well as drug resistance.
  
  
  METHODS
  We synthesized a new compound carrying: (i) Neu5Acα2-6Galβ1-4GlcNAc (6SLN) for targeting immutable haemagglutinins (HAs) unless switched from human-type receptor preference; (ii) an acyl chain (lipo) for locking the compound with the viral HA via hydrophobic interactions; and (iii) a flexible poly-α-L-glutamic acid (PGA) for enhancing the compound solubility and for coating the viral surface, precluding accessibility of the PGA-coated virus to the negatively charged sialic acid on the host cell surface.
  
  
  RESULTS
  6SLN-lipo PGA appears to subvert binding of pandemic H1 and seasonal H3 HAs to receptors, as assessed by using guinea pig erythrocytes, which is critical for virus entry into host cells for multiplication. It shows high potency with IC50 values in the range of 300-500 nM against multiplication of both influenza pandemic H1N1/2009 and seasonal H3N2/2004 viruses in cell culture. It acts in synergism with either of the two FDA-approved neuraminidase inhibitor (NAI) clinical drugs, zanamivir (Relenza(®)) and oseltamivir carboxylate (active form of Tamiflu(®)), and it has the potential to aid NAI drugs to achieve complete clearance of the virus from the culture.
  
  
  CONCLUSIONS
  6SLN-lipo PGA is a new potential candidate drug for influenza control and is an attractive candidate for use in combination with an NAI drug for minimized toxicity, delayed development of resistance, prevention and treatment with the potential for eradication of human influenza.
authors.affiliation: Department of Preclinical Sciences, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12120, Thailand College of Life and Health Sciences, Chubu University, Aichi 487-8501, Japan snongluk@hotmail.com.
authors.forename: Nongluk
authors.initials: N
authors.lastname: Sriwilaijaroen
authors.affiliation: Synthetic Cellular Chemistry Laboratory, RIKEN, Saitama 351-0198, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Takashita
authors.affiliation: College of Life and Health Sciences, Chubu University, Aichi 487-8501, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hiramatsu
authors.affiliation: Institute of Glycoscience, Tokai University, Kanagawa 259-1292, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kanie
authors.affiliation: College of Life and Health Sciences, Chubu University, Aichi 487-8501, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000821:virology; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D020128:Inhibitory Concentration 50; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors*; D053585:Virus Attachment / Q000187:drug effects
chemical_list: C000608519:6SLN-lipo PGA; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006017:Glycolipids; D011991:Receptors, Virus; D014764:Viral Proteins; D011099:Polyglutamic Acid; C487630:NA protein, influenza A virus; D009439:Neuraminidase