Binding inhibition of various influenza viruses by sialyllactose-modified trimer DNAs

Bioorg Med Chem Lett. 2019 Mar 1;29(5):744-748. doi: 10.1016/j.bmcl.2018.12.064. Epub 2019 Jan 2.

Abstract

Sialyllactose (SL)-modified trimer DNAs with a similar SL presentation as their binding sites on influenza virus hemagglutinin (HA) trimer were designed and synthesized. These trimer DNAs showed high affinity for various influenza viruses, including A/Puerto Rico/08/34 (H1N1), A/Beijing/262/95 (H1N1), A/Yokohama/77/2008 (H1N1), and A/Panama/2007/99 (H3N2). Thus, presentation of SL residues on three vertexes of the scaffold as well as sialic acid binding sites on the HA trimer regardless of a tri-branched or triangular scaffold are important for high affinity for influenza viruses. These compounds have the potential for use in detection and as inhibitors of a broad spectrum of influenza viruses.

Keywords: DNA scaffold; Hemagglutinin; Influenza virus; Sialic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • DNA / chemistry
  • DNA / pharmacology*
  • Humans
  • Influenza A virus / drug effects*
  • Influenza A virus / metabolism
  • Lactose / analogs & derivatives*
  • Lactose / chemistry
  • Sialic Acids / chemistry*
  • Virus Attachment / drug effects*

Substances

  • Antiviral Agents
  • Sialic Acids
  • N-acetylneuraminoyllactose
  • DNA
  • Lactose