TY - JOUR
T1 - Evaluation of the activity of lamivudine and zidovudine against ebola virus
AU - Cong, Yu
AU - Dyall, Julie
AU - Hart, Brit J.
AU - DeWald, Lisa Evans
AU - Johnson, Joshua C.
AU - Postnikova, Elena
AU - Zhou, Huanying
AU - Gross, Robin
AU - Rojas, Oscar
AU - Alexander, Isis
AU - Josleyn, Nicole
AU - Zhang, Tengfei
AU - Michelotti, Julia
AU - Janosko, Krisztina
AU - Glass, Pamela J.
AU - Flint, Mike
AU - McMullan, Laura K.
AU - Spiropoulou, Christina F.
AU - Mierzwa, Tim
AU - Guha, Rajarshi
AU - Shinn, Paul
AU - Michael, Sam
AU - Klumpp-Thomas, Carleen
AU - McKnight, Crystal
AU - Thomas, Craig
AU - Eakin, Ann E.
AU - O'Loughlin, Kathleen G.
AU - Green, Carol E.
AU - Catz, Paul
AU - Mirsalis, Jon C.
AU - Honko, Anna N.
AU - Olinger, Gene G.
AU - Bennett, Richard S.
AU - Holbrook, Michael R.
AU - Hensley, Lisa E.
AU - Jahrling, Peter B.
N1 - Publisher Copyright:
© This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2016/11
Y1 - 2016/11
N2 - In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B virus infections. According to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from Ebola virus disease. In this study, the anti-Ebola virus (EBOV) activity of lamivudine and another antiretroviral, zidovudine, were evaluated in a diverse set of cell lines against two variants of wild-type EBOV. Variable assay parameters were assessed to include different multiplicities of infection, lengths of inoculation times, and durations of dosing. At a multiplicity of infection of 1, lamivudine and zidovudine had no effect on EBOV propagation in Vero E6, Hep G2, or HeLa cells, or in primary human monocyte-derived macrophages. At a multiplicity of infection of 0.1, zidovudine demonstrated limited anti-EBOV activity in Huh 7 cells. Under certain conditions, lamivudine had low anti-EBOV activity at the maximum concentration tested (320 μM). However, lamivudine never achieved greater than 30% viral inhibition, and the activity was not consistently reproducible. Combination of lamivudine and zidovudine showed no synergistic antiviral activity. Independently, a set of in vitro experiments testing lamivudine and zidovudine for antiviral activity against an Ebolaenhanced green fluorescent protein reporter virus was performed at the Centers for Disease Control and Prevention. No antiviral activity was observed for either compound. A study evaluating the efficacy of lamivudine in a Guinea pig model of EVD found no survival benefit. This lack of benefit was observed despite plasma lamivudine concentrations in Guinea pig of about 4 μg/ml obtained in a separately conducted pharmacokinetics study. These studies found no evidence to support the therapeutic use of lamivudine for the treatment of EVD.
AB - In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B virus infections. According to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from Ebola virus disease. In this study, the anti-Ebola virus (EBOV) activity of lamivudine and another antiretroviral, zidovudine, were evaluated in a diverse set of cell lines against two variants of wild-type EBOV. Variable assay parameters were assessed to include different multiplicities of infection, lengths of inoculation times, and durations of dosing. At a multiplicity of infection of 1, lamivudine and zidovudine had no effect on EBOV propagation in Vero E6, Hep G2, or HeLa cells, or in primary human monocyte-derived macrophages. At a multiplicity of infection of 0.1, zidovudine demonstrated limited anti-EBOV activity in Huh 7 cells. Under certain conditions, lamivudine had low anti-EBOV activity at the maximum concentration tested (320 μM). However, lamivudine never achieved greater than 30% viral inhibition, and the activity was not consistently reproducible. Combination of lamivudine and zidovudine showed no synergistic antiviral activity. Independently, a set of in vitro experiments testing lamivudine and zidovudine for antiviral activity against an Ebolaenhanced green fluorescent protein reporter virus was performed at the Centers for Disease Control and Prevention. No antiviral activity was observed for either compound. A study evaluating the efficacy of lamivudine in a Guinea pig model of EVD found no survival benefit. This lack of benefit was observed despite plasma lamivudine concentrations in Guinea pig of about 4 μg/ml obtained in a separately conducted pharmacokinetics study. These studies found no evidence to support the therapeutic use of lamivudine for the treatment of EVD.
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U2 - 10.1371/journal.pone.0166318
DO - 10.1371/journal.pone.0166318
M3 - Article
C2 - 27902714
AN - SCOPUS:85000502070
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 11
M1 - e0166318
ER -