Preliminary Evaluation of the Effect of Investigational Ebola Virus Disease Treatments on Viral Genome Sequences

Abstract

Background: 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.

Methods: 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.

Results: We observed no major or minor EBOV mutations within regions targeted by therapeutics.

Conclusions: 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.

Keywords: Ebola virus; antiviral agents; directed molecular evolution; high-throughput nucleotide sequencing; molecular epidemiology.