Artículos de revistas
Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
Fecha
2015-09Registro en:
Gray, William T.; Frey, Kathleen M.; Laskey, Sarah B.; Mislak, Andrea C.; Spasov, Krasimir A.; et al.; Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance; American Chemical Society; ACS Medicinal Chemistry Letters; 6; 10; 9-2015; 1075-1079
1948-5875
Autor
Gray, William T.
Frey, Kathleen M.
Laskey, Sarah B.
Mislak, Andrea C.
Spasov, Krasimir A.
Lee, Won Gil
Bollini, Mariela
Siliciano, Robert F.
Jorgensen, William L.
Anderson, Karen S.
Resumen
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.