Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells

J Virol. 2004 Oct;78(20):11334-9. doi: 10.1128/JVI.78.20.11334-11339.2004.

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 microM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Cell Line
  • China
  • Chlorocebus aethiops
  • Chromatography, Affinity
  • Flavonoids / pharmacology*
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • Humans
  • Hydrolyzable Tannins / chemistry
  • Hydrolyzable Tannins / pharmacology*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Luteolin
  • Mass Spectrometry
  • Membrane Glycoproteins / metabolism
  • Microbial Sensitivity Tests
  • Plants, Medicinal / chemistry*
  • Plants, Medicinal / metabolism
  • SARS Virus / drug effects*
  • SARS Virus / pathogenicity*
  • Spike Glycoprotein, Coronavirus
  • Vero Cells
  • Viral Envelope Proteins / metabolism

Substances

  • Antiviral Agents
  • Flavonoids
  • Hydrolyzable Tannins
  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • Luciferases
  • Luteolin