Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.

Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drug...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rui-Rui Wang, Qing-Hua Yang, Rong-Hua Luo, You-Mei Peng, Shao-Xing Dai, Xing-Jie Zhang, Huan Chen, Xue-Qing Cui, Ya-Juan Liu, Jing-Fei Huang, Jun-Biao Chang, Yong-Tang Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8e561f28d7a41c593c31bb9655dd0f1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f8e561f28d7a41c593c31bb9655dd0f1
record_format	dspace
spelling	oai:doaj.org-article:f8e561f28d7a41c593c31bb9655dd0f12021-11-25T06:03:42ZAzvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.1932-620310.1371/journal.pone.0105617https://doaj.org/article/f8e561f28d7a41c593c31bb9655dd0f12014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25144636/?tool=EBIhttps://doaj.org/toc/1932-6203Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC(50)s ranging from 0.03 to 6.92 nM) and HIV-2 (EC(50)s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. The present data demonstrates the potential of azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range.Rui-Rui WangQing-Hua YangRong-Hua LuoYou-Mei PengShao-Xing DaiXing-Jie ZhangHuan ChenXue-Qing CuiYa-Juan LiuJing-Fei HuangJun-Biao ChangYong-Tang ZhengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e105617 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rui-Rui Wang Qing-Hua Yang Rong-Hua Luo You-Mei Peng Shao-Xing Dai Xing-Jie Zhang Huan Chen Xue-Qing Cui Ya-Juan Liu Jing-Fei Huang Jun-Biao Chang Yong-Tang Zheng Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
description	Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC(50)s ranging from 0.03 to 6.92 nM) and HIV-2 (EC(50)s ranging from 0.018 to 0.025 nM). It also showed synergism in combination with six approved anti-HIV drugs on both C8166 and PBMC. In combination assay, the concentrations of azvudine used were 1000 or 500 fold lower than other drugs. Azvudine also showed potent inhibition on NRTI-resistant strains (L74V and T69N). Although M184V caused 250 fold reduction in susceptibility, azvudine remained active at nanomolar range. In in vitro induced resistant assay, the frequency of M184I mutation increased with induction time which suggests M184I as the key mutation in azvudine treatment. As control, lamivudine treatment resulted in a higher frequency of M184I/V given the same induction time and higher occurrence of M184V was found. Molecular modeling analysis suggests that steric hindrance is more pronounced in mutant M184I than M184V due to the azido group of azvudine. The present data demonstrates the potential of azvudine as a complementary drug to current anti-HIV drugs. M184I should be the key mutation, however, azvudine still remains active on HIV-1LAI-M184V at nanomolar range.
format	article
author	Rui-Rui Wang Qing-Hua Yang Rong-Hua Luo You-Mei Peng Shao-Xing Dai Xing-Jie Zhang Huan Chen Xue-Qing Cui Ya-Juan Liu Jing-Fei Huang Jun-Biao Chang Yong-Tang Zheng
author_facet	Rui-Rui Wang Qing-Hua Yang Rong-Hua Luo You-Mei Peng Shao-Xing Dai Xing-Jie Zhang Huan Chen Xue-Qing Cui Ya-Juan Liu Jing-Fei Huang Jun-Biao Chang Yong-Tang Zheng
author_sort	Rui-Rui Wang
title	Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
title_short	Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
title_full	Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
title_fullStr	Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
title_full_unstemmed	Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
title_sort	azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f8e561f28d7a41c593c31bb9655dd0f1
work_keys_str_mv	AT ruiruiwang azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT qinghuayang azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT ronghualuo azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT youmeipeng azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT shaoxingdai azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT xingjiezhang azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT huanchen azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT xueqingcui azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT yajuanliu azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT jingfeihuang azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT junbiaochang azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro AT yongtangzheng azvudineanovelnucleosidereversetranscriptaseinhibitorshowedgooddrugcombinationfeaturesandbetterinhibitionondrugresistantstrainsthanlamivudineinvitro
_version_	1718414258334597120

Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.

Ejemplares similares