title: Therapeutics for filovirus infection: traditional approaches and progress towards in silico drug design.
abstract: BACKGROUND
  Ebolaviruses and marburgviruses cause severe and often lethal human hemorrhagic fevers. As no FDA-approved therapeutics are available for these infections, efforts to discover new therapeutics are important, especially because these pathogens are considered biothreats and emerging infectious diseases. All methods for discovering new therapeutics should be considered, including compound library screening in vitro against virus and in silico structure-based drug design, where possible, if sufficient biochemical and structural information is available.
  
  
  METHODS
  This review covers the structure and function of filovirus proteins, as they have been reported to date, as well as some of the current antiviral screening approaches. The authors discuss key studies mapping small-molecule modulators that were found through library and in silico screens to potential sites on viral proteins or host proteins involved in virus trafficking and pathogenesis. A description of ebolavirus and marburgvirus diseases and available animal models is also presented.
  
  
  CONCLUSIONS
  To discover novel therapeutics with potent efficacy using sophisticated computational methods, more high-resolution crystal structures of filovirus proteins and more details about the protein functions and host interaction will be required. Current compound screening efforts are finding active antiviral compounds, but an emphasis on discovery research to investigate protein structures and functions enabling in silico drug design would provide another avenue for finding antiviral molecules. Additionally, targeting of protein-protein interactions may be a future avenue for drug discovery since disrupting catalytic sites may not be possible for all proteins.
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Integrated Toxicology Division, Fort Detrick, 1425 Porter Street, Frederick, MD 21702, USA. amy.c.shurtleff.ctr@us.army.mil
authors.forename: Amy C
authors.initials: AC
authors.lastname: Shurtleff
authors.forename: Tam L
authors.initials: TL
authors.lastname: Nguyen
authors.forename: David A
authors.initials: DA
authors.lastname: Kingery
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003198:Computer Simulation; D015195:Drug Design; D016563:Filoviridae; D018702:Filoviridae Infections / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins