Abstract
Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavirenz and rilpivirine. Kinetic data suggests that RT (K101P) variants are as catalytically fit as wild-type and thus can potentially increase in the viral population as more antiviral regimens include efavirenz or rilpivirine. Comparison of wild-type structures and a new crystal structure of RT (K101P) in complex with a leading compound confirms that the K101P mutation is not a liability for the catechol diethers while suggesting that key interactions are lost with efavirenz and rilpivirine.
Original language | English (US) |
---|---|
Pages (from-to) | 1075-1079 |
Number of pages | 5 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 6 |
Issue number | 10 |
DOIs | |
State | Published - Oct 8 2015 |
Keywords
- HIV
- mutations
- non-nucleoside reverse transcriptase inhibitors
- resistance
- reverse transcriptase
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry