Novel Polyanions Inhibiting Replication of Influenza Viruses

Antimicrob Agents Chemother. 2016 Mar 25;60(4):1955-66. doi: 10.1128/AAC.02183-15. Print 2016 Apr.

Abstract

Novel sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) and N-sulfonated chitosan (NSCH) have been synthesized, and their activity against influenza A and B viruses has been studied and compared with that of a series of carrageenans, marine polysaccharides of well-documented anti-influenza activity. NSPAHs were found to be nontoxic and very soluble in water, in contrast to gel-forming and thus generally poorly soluble carrageenans.In vitroandex vivostudies using susceptible cells (Madin-Darby canine kidney epithelial cells and fully differentiated human airway epithelial cultures) demonstrated the antiviral effectiveness of NSPAHs. The activity of NSPAHs was proportional to the molecular mass of the chain and the degree of substitution of amino groups with sulfonate groups. Mechanistic studies showed that the NSPAHs and carrageenans inhibit influenza A and B virus assembly in the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / pharmacology*
  • Chitosan / chemical synthesis
  • Chitosan / pharmacology*
  • Dogs
  • Epithelial Cells / drug effects
  • Epithelial Cells / virology
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / growth & development
  • Influenza A Virus, H3N2 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / genetics
  • Influenza A Virus, H3N2 Subtype / growth & development
  • Influenza B virus / drug effects*
  • Influenza B virus / genetics
  • Influenza B virus / growth & development
  • Inhibitory Concentration 50
  • Madin Darby Canine Kidney Cells
  • Polyamines / chemical synthesis
  • Polyamines / pharmacology*
  • Polyelectrolytes
  • Polymers / chemical synthesis
  • Polymers / pharmacology*
  • RNA, Viral / antagonists & inhibitors
  • RNA, Viral / biosynthesis
  • Structure-Activity Relationship
  • Sulfuric Acid Esters / chemical synthesis
  • Sulfuric Acid Esters / pharmacology*
  • Virus Assembly / drug effects
  • Virus Attachment / drug effects
  • Virus Inactivation / drug effects
  • Virus Internalization / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Polyamines
  • Polyelectrolytes
  • Polymers
  • RNA, Viral
  • Sulfuric Acid Esters
  • polyanions
  • polyallylamine
  • Chitosan

Grants and funding

Foundation for Polish Science provided funding to Justyna Ciejka under grant number VENTURES/2013-11/1 cofinanced by the EU European Regional Development Fund. K.P. acknowledges a networking contribution by the COST Action CM1407 (“Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery”). Parts of this research were carried out with equipment purchased thanks to the financial support of European Union structural funds (grants POIG.02.01.00-12-064/08 and POIG.02.01.00-12-167/08). The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University is a partner of the Leading National Research Center supported by the Ministry of Science and Higher Education of the Republic of Poland. The funders had no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.