The antiviral compound enviroxime targets the 3A coding region of rhinovirus and poliovirus

J Virol. 1995 Jul;69(7):4189-97. doi: 10.1128/JVI.69.7.4189-4197.1995.


Enviroxime is an antiviral compound that inhibits the replication of rhinoviruses and enteroviruses. We have explored the mechanism of action of enviroxime by using poliovirus type 1 and human rhinovirus type 14 as model systems. By varying the time of drug addition to virus-infected cells, we determined that enviroxime could be added several hours postinfection without significant loss of inhibition. This suggested that the drug targeted a step involved in RNA replication or protein processing. To identify this target, we mapped 23 independent mutations in mutants that could multiply in the presence of 1 microgram of enviroxime per ml. Each of these mutants contained a single nucleotide substitution that altered one amino acid in the 3A coding region. Using oligonucleotide-directed mutagenesis of cDNA clones, we have confirmed that these single-amino-acid substitutions are sufficient to confer the resistance phenotype. In addition, we conducted two experiments to support the hypothesis that enviroxime inhibits a 3A function. First, we determined by dot blot analysis of RNA from poliovirus-infected cells that enviroxime preferentially inhibits synthesis of the viral plus strand. Second, we demonstrated that enviroxime inhibits the initiation of plus-strand RNA synthesis as measured by the addition of [32P]uridine to 3AB in poliovirus crude replication complexes. To our knowledge, this is the first evidence that 3A can be targeted by antiviral drugs. We anticipate that enviroxime will be a useful tool for investigating the natural function of the 3A protein.

MeSH terms

  • Amino Acid Sequence
  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Benzimidazoles / pharmacology*
  • Drug Resistance
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oximes
  • Poliovirus / drug effects*
  • Poliovirus / genetics
  • RNA, Viral / antagonists & inhibitors
  • RNA, Viral / biosynthesis
  • Rhinovirus / drug effects*
  • Rhinovirus / genetics
  • Sulfonamides
  • Uridine / metabolism
  • Viral Core Proteins / genetics*
  • Viral Core Proteins / physiology


  • Antiviral Agents
  • Benzimidazoles
  • Oximes
  • RNA, Viral
  • Sulfonamides
  • Viral Core Proteins
  • viroxime
  • Uridine