Investigating Human Immunodeficiency Virus Resistance Mechanisms to D-Peptide Entry Inhibitors

Amanda Ray Smith
The PIE series of D-peptide HIV entry inhibitors, PIE12-trimer and Chol-PIE12-trimer (CPT31), inhibit a wide range of HIV isolates with pM potency while also exhibiting a high barrier to resistance. Here, we show that HIV acquires a primary PIE12 resistance mutation (Q577R/N/K) in both in vitro and in vivo resistance models. Development of this resistance mutation comes at a significant fitness cost to the virus, but the virus also acquires a set of compensatory mutations...
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