Mode of interference of trisodium phosphonoformate (INN: foscarnet sodium), with influenza virus mRNA synthesis

Virology
|May 1, 1984
PubMed

Insights

Foscarnet noncompetitively inhibits influenza RNA polymerase, blocking mRNA elongation after the conserved sequence initiation. This antiviral mechanism affects viral RNA synthesis.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Foscarnet is known to inhibit influenza RNA polymerase.
  • The precise mechanism of foscarnet's inhibition requires further elucidation.

Purpose of the Study:

  • To investigate the mode of inhibition of foscarnet on influenza RNA polymerase.
  • To analyze the effects of foscarnet on mRNA synthesis initiation and elongation.

Main Methods:

  • Enzyme-kinetic procedures were employed.
  • Product analysis was conducted to determine inhibition patterns.

Main Results:

  • Foscarnet exhibited noncompetitive inhibition against ATP, CTP, and UTP.
  • Mixed inhibition was observed with respect to GTP.
  • Foscarnet inhibited mRNA elongation but not initiation, specifically after the conserved 5' sequence.

Conclusions:

  • Foscarnet acts as a mixed inhibitor of influenza RNA polymerase.
  • The drug blocks viral mRNA formation by inhibiting the elongation step.
  • This inhibition occurs post-initiation, after the synthesis of the conserved 12-nucleotide sequence.

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