title: In vitro inhibition of influenza A virus infection by marine microalga-derived sulfated polysaccharide p-KG03.
abstract: The sulfated polysaccharide, p-KG03, purified from the marine microalga, Gyrodinium impudium, is a unique compound comprising homogenous galactose units conjugated to uronic acid and sulfated groups. Although previous studies showed that p-KG03 suppresses tumor cell growth and infection by encephalomyocarditis virus, its effect against enveloped virus infection and the biological mechanism of action have not been elucidated. In this report, the inhibitory activity of p-KG03 against influenza virus was examined and compared with that of other sulfated polysaccharides (fucoidan and pentosan polysulfate) and antiviral agents (oseltamivir phosphate, oseltamivir carboxylate, amantadine, and ribavirin). The results of a cytopathic effect reduction assay using MDCK cells demonstrated that p-KG03 exhibited the 50% effective concentration (EC(50)) values of 0.19-0.48 μg/ml against influenza type A virus infection (selectivity index >200) but not all influenza type B viruses. Mechanism studies showed that inhibition of influenza virus replication was maximized when p-KG03 was added during or within 6 h after viral infection, suggesting that mainly the viral adsorption and internalization steps are targeted by this compound. The results of influenza virus binding assay to p-KG03 and fluorescence microscopy indicate that the antiviral activity of p-KG03 is directly associated with its interaction with viral particles. The sulfated polysaccharide p-KG03 is a potent and specific influenza A viral entry inhibitor and may be a candidate for antiviral drug development.
authors.affiliation: Virus Research and Testing Team, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, South Korea.
authors.forename: Meehyein
authors.initials: M
authors.lastname: Kim
authors.affiliation: Polar Life Science, Korea Polar Research Institute, Songdo-dong, Yeonsu-gu, Incheon 406-840, South Korea.
authors.forename: Joung Han
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Virus Research and Testing Team, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, South Korea.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Virus Research and Testing Team, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, South Korea.
authors.forename: Hae Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Virus Research and Testing Team, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, South Korea.
authors.forename: Woo Ghil
authors.initials: WG
authors.lastname: Lee
authors.affiliation: Polar Life Science, Korea Polar Research Institute, Songdo-dong, Yeonsu-gu, Incheon 406-840, South Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Polar Life Science, Korea Polar Research Institute, Songdo-dong, Yeonsu-gu, Incheon 406-840, South Korea.
authors.forename: Pil-Sung
authors.initials: PS
authors.lastname: Kang
authors.affiliation: Virus Research and Testing Team, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, South Korea. Electronic address: ckyolee@krict.re.kr.
authors.forename: Chong-Kyo
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D009981:Influenza B virus / Q000187:drug effects / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology*; D058086:Microalgae / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D000461:Rhodophyta / Q000737:chemistry*; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011134:Polysaccharides