Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance

Autores
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.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Gray, William T.. University of Yale; Estados Unidos
Fil: Frey, Kathleen M.. University of Yale; Estados Unidos
Fil: Laskey, Sarah B.. University Johns Hopkins; Estados Unidos
Fil: Mislak, Andrea C.. University of Yale; Estados Unidos
Fil: Spasov, Krasimir A.. University of Yale; Estados Unidos
Fil: Lee, Won Gil. University of Yale; Estados Unidos
Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos
Fil: Siliciano, Robert F.. University Johns Hopkins; Estados Unidos. Howard Hughes Medial Institute; Estados Unidos
Fil: Jorgensen, William L.. University of Yale; Estados Unidos
Fil: Anderson, Karen S.. University of Yale; Estados Unidos
Materia
HIV
Rreverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Resistance
Mutations
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15923
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/15923
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistanceGray, William T.Frey, Kathleen M.Laskey, Sarah B.Mislak, Andrea C.Spasov, Krasimir A.Lee, Won GilBollini, MarielaSiliciano, Robert F.Jorgensen, William L.Anderson, Karen S.HIVRreverse transcriptaseNon-nucleoside reverse transcriptase inhibitorsResistanceMutationshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Catechol 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.Fil: Gray, William T.. University of Yale; Estados UnidosFil: Frey, Kathleen M.. University of Yale; Estados UnidosFil: Laskey, Sarah B.. University Johns Hopkins; Estados UnidosFil: Mislak, Andrea C.. University of Yale; Estados UnidosFil: Spasov, Krasimir A.. University of Yale; Estados UnidosFil: Lee, Won Gil. University of Yale; Estados UnidosFil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados UnidosFil: Siliciano, Robert F.. University Johns Hopkins; Estados Unidos. Howard Hughes Medial Institute; Estados UnidosFil: Jorgensen, William L.. University of Yale; Estados UnidosFil: Anderson, Karen S.. University of Yale; Estados UnidosAmerican Chemical Society2015-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15923Gray, 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; 1075-10791948-5875enginfo:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.5b00254info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsmedchemlett.5b00254info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601059/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:58Zoai:ri.conicet.gov.ar:11336/15923instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:23:58.886CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
title Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
spellingShingle Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
Gray, William T.
HIV
Rreverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Resistance
Mutations
title_short Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
title_full Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
title_fullStr Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
title_full_unstemmed Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
title_sort Potent inhibitors active against HIV reverse transcriptase with K101P, a mutation conferring rilpivirine resistance
dc.creator.none.fl_str_mv 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.
author Gray, William T.
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HIV
Rreverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Resistance
Mutations
topic HIV
Rreverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Resistance
Mutations
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Gray, William T.. University of Yale; Estados Unidos
Fil: Frey, Kathleen M.. University of Yale; Estados Unidos
Fil: Laskey, Sarah B.. University Johns Hopkins; Estados Unidos
Fil: Mislak, Andrea C.. University of Yale; Estados Unidos
Fil: Spasov, Krasimir A.. University of Yale; Estados Unidos
Fil: Lee, Won Gil. University of Yale; Estados Unidos
Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Yale; Estados Unidos
Fil: Siliciano, Robert F.. University Johns Hopkins; Estados Unidos. Howard Hughes Medial Institute; Estados Unidos
Fil: Jorgensen, William L.. University of Yale; Estados Unidos
Fil: Anderson, Karen S.. University of Yale; Estados Unidos
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15923
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
url http://hdl.handle.net/11336/15923
identifier_str_mv 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
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/acsmedchemlett.5b00254
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acsmedchemlett.5b00254
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601059/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614236072837120
score 13.070432

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