Chemical characteristics, mechanism of action and antiviral activity of etravirine

Enfermedades infecciosas y microbiología clínica
Federico García GarcíaVicente Guillot Suay

Abstract

Etravirine (ETR) is a diarylpyrimidine derivative with a polycyclic molecule composed of 3 aromatic rings with single bonds between the rings (C(20)H(15)BrN(60)). The drug acts through a mechanism of noncompetitive inhibition on binding to a hydrophobic binding pocket, very close to the active center of the enzyme, provoking an allosteric transition to a conformation that distorts its structure and impedes DNA polymerization. The 3 rings with single bonds between the rings confer the molecule with great fl exibility and torsion. Because of these characteristics, etravirine can adapt to conformational changes in the binding pocket, including a large number of the conformations provoked by the resistance mutations that appear after failure to regimens that include efavirenz or nevirapine. This specific chemical structure largely explains the drug's distinguishing features in terms of its antiviral potency and high genetic barrier. ETR is a highly active molecule against HIV-1. This drug has a high genetic barrier to resistance and has demonstrated antiviral activity against a wide panel of recombinant viruses that incorporate resistance mutations to first-generation non-nucleoside analogues. Equally, ETR has demonstrated efficacy...Continue Reading

References

Apr 1, 1995·Nature Structural Biology·R EsnoufD Stuart
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·G TachedjianS P Goff
Jul 30, 2008·Expert Review of Anti-infective Therapy·E SeminariA Lazzarin

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