Candidate Medical Countermeasures Targeting Ebola Virus Cell Entry

Abstract

Medical countermeasures (MCMs) against virus infections ideally prevent the adsorption or entry of virions into target cells, thereby circumventing infection. Recent significant advances in elucidating the mechanism of Ebola virus (EBOV) host-cell penetration include the involvement of two-pore channels at the early stage of entry, and identification of cellular proteases for EBOV spike glycoprotein maturation and the intracellular EBOV receptor, Niemann–Pick type C1. This improved understanding of the initial steps of EBOV infection is now increasingly applied to rapid development of candidate MCMs, some of which have already entered the clinic. Candidate MCMs discussed include antibodies, small molecules and peptides that target various stages of the described EBOV cell-entry pathway. In this review, we summarize the currently known spectrum of EBOV cell-entry inhibitors, describe their mechanism of action and evaluate their potential for future development.

KEYWORDS :

• antibody therapeutics
• antiviral
• Ebola virus
• ebolavirus
• EBOV
• entry inhibitor
• Filoviridae
• filovirus
• glycoprotein
• MCM
• medical countermeasure
• VHF
• viral hemorrhagic fever
• virus cell entry

Disclaimer

The views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the US Department of the Army, the US Department of Defense, the US Department of Health and Human Services, or of the institutions and companies affiliated with the authors.

Financial & competing interests disclosure

This work was supported in part through Battelle Memorial Institute’s prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract no. HHSN272200700016I. J Liang, L Bollinger, J Wada, and KS Jensen performed this work as employees of Battelle Memorial Institute. A subcontractor to Battelle Memorial Institute who performed this work is JH Kuhn, an employee of Tunnell Government Services, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.