Synthetic sulfonated derivatives of poly(allylamine hydrochloride) as inhibitors of human metapneumovirus

PLoS One. 2019 Mar 28;14(3):e0214646. doi: 10.1371/journal.pone.0214646. eCollection 2019.

Abstract

Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Humans
  • Metapneumovirus / drug effects*
  • Metapneumovirus / physiology
  • Polyamines / chemical synthesis
  • Polyamines / chemistry*
  • Polyamines / pharmacology*
  • Sulfonic Acids / chemistry*
  • Virion / drug effects
  • Virion / physiology
  • Virus Internalization / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Polyamines
  • Sulfonic Acids
  • polyallylamine

Grants and funding

This work was supported by grants from the National Science Center (UMO- 2012/07/E/NZ6/01712 and UMO-2016/21/D/ST5/01661) (KP and JC, respectively), grant Lider/27/55/L-2/10/2011 (to KP) from the National Centre for Research and Development, Foundation for Polish Science provided funding to JC under grant number VENTURES/2013-11/1 cofinanced by the EU European Regional Development Fund. KP would like to acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by nature - from natural products chemistry to drug discovery” from European Cooperation in Science and Technology. The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University is a beneficiary of the structural funds from the European Union (grant No: POIG.02.01.00-12-064/08 – “Molecular biotechnology for health”). 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, decision to publish, or preparation of the manuscript.