title: Preliminary Evaluation of the Effect of Investigational Ebola Virus Disease Treatments on Viral Genome Sequences.
abstract: Several patients with Ebola virus disease (EVD) managed in the United States have received ZMapp monoclonal antibodies, TKM-Ebola small interfering RNA, brincidofovir, and/or convalescent plasma as investigational therapeutics.
  
  
  
  To investigate whether treatment selected for Ebola virus (EBOV) mutations conferring resistance, viral sequencing was performed on RNA extracted from clinical blood specimens from patients with EVD following treatment, and putative viral targets were analyzed.
  
  
  
  We observed no major or minor EBOV mutations within regions targeted by therapeutics.
  
  
  
  This small subset of patients and clinical specimens suggests that evolution of resistance is not a direct consequence of antiviral treatment. As EVD antiviral treatments are introduced into wider use, it is essential that continuous viral full-genome surveillance is performed, to monitor for the emergence of escape mutations.
authors: Viral Special Pathogens Branch.
authors: Shannon L M
authors: SL
authors: Whitmer
authors: Viral Special Pathogens Branch.
authors: César
authors: C
authors: Albariño
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Samuel S
authors: SS
authors: Shepard
authors: Institute of Evolutionary Biology, University of Edinburgh, United Kingdom.
authors: Gytis
authors: G
authors: Dudas
authors: Biotechnology Core Facility Branch.
authors: Mili
authors: M
authors: Sheth
authors: Viral Special Pathogens Branch.
authors: Shelley C
authors: SC
authors: Brown
authors: Viral Special Pathogens Branch.
authors: Deborah
authors: D
authors: Cannon
authors: Viral Special Pathogens Branch.
authors: Bobbie R
authors: BR
authors: Erickson
authors: Viral Special Pathogens Branch.
authors: Aridth
authors: A
authors: Gibbons
authors: Viral Special Pathogens Branch.
authors: Amy
authors: A
authors: Schuh
authors: Viral Special Pathogens Branch.
authors: Tara
authors: T
authors: Sealy
authors: Viral Special Pathogens Branch.
authors: Elizabeth
authors: E
authors: Ervin
authors: Biotechnology Core Facility Branch.
authors: Mike
authors: M
authors: Frace
authors: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Timothy M
authors: TM
authors: Uyeki
authors: Viral Special Pathogens Branch.
authors: Stuart T
authors: ST
authors: Nichol
authors: Viral Special Pathogens Branch.
authors: Ute
authors: U
authors: Ströher
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D003289:Convalescence; D024882:Drug Resistance, Viral; D029043:Ebolavirus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D016679:Genome, Viral / Q000235:genetics*; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation; D010949:Plasma; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D034741:RNA, Small Interfering
keywords: Ebola virus; antiviral agents; directed molecular evolution; high-throughput nucleotide sequencing; molecular epidemiology