1 research outputs found
Rational Design of Potent Non-Nucleoside Inhibitors of HIV‑1 Reverse Transcriptase
A new series of non-nucleoside reverse transcriptase
inhibitors
based on an imidazole-amide biarylether scaffold has been identified
and shown to possess potent antiviral activity against HIV-1, including
the NNRTI-resistant Y188L mutated virus. X-ray crystallography of
inhibitors bound to reverse transcriptase, including a structure of
the Y188L RT protein, was used extensively to help identify and optimize
the key hydrogen-bonding motif. This led directly to the design of
compound <b>43</b> that exhibits remarkable antiviral activity
(EC<sub>50</sub> < 1 nM) against a wide range of NNRTI-resistant
viruses and a favorable pharmacokinetic profile across multiple species