[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
PLoS One. 2016 Nov 30;11(11):e0166318. doi: 10.1371/journal.pone.0166318. eCollection 2016.
Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus.
Cong Y1, Dyall J1, Hart BJ1, DeWald LE1, Johnson JC1, Postnikova E1, Zhou H1, Gross R1, Rojas O1, Alexander I1, Josleyn N1, Zhang T1, Michelotti J1, Janosko K1, Glass PJ2, Flint M3, McMullan LK3, Spiropoulou CF3, Mierzwa T4, Guha R4, Shinn P4, Michael S4, Klumpp-Thomas C4, McKnight C4, Thomas C4, Eakin AE5, O’Loughlin KG6, Green CE6, Catz P6, Mirsalis JC6, Honko AN1, Olinger GG Jr1, Bennett RS1, Holbrook MR1, Hensley LE1, Jahrling PB1,7.
Author information: 1Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, United States of America. 2United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America. 3Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. 4The National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, United States of America. 5Office of Biodefense, Research Resources & Translational Research, Division of Microbiology & Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America. 6SRI International, Menlo Park, California, United States of America. 7Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, United States of America.
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 Ebola-enhanced 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.
PMID: 27902714 DOI: 10.1371/journal.pone.0166318
[PubMed – in process]
Keywords: Ebola; Antivirals; Lamivudine; Zidovudine.