title: Filovirus proteins for antiviral drug discovery: Structure/function bases of the replication cycle.
abstract: Filoviruses are important pathogens that cause severe and often fatal hemorrhagic fever in humans, for which no approved vaccines and antiviral treatments are yet available. In an earlier article (Martin et al., Antiviral Research, 2016), we reviewed the role of the filovirus surface glycoprotein in replication and as a target for drugs and vaccines. In this review, we focus on recent findings on the filovirus replication machinery and how they could be used for the identification of new therapeutic targets and the development of new antiviral compounds. First, we summarize the recent structural and functional advances on the molecules involved in filovirus replication/transcription cycle, particularly the NP, VP30, VP35 proteins, and the "large" protein L, which harbors the RNA-dependent RNA polymerase (RdRp) and mRNA capping activities. These proteins are essential for viral mRNA synthesis and genome replication, and consequently they constitute attractive targets for drug design. We then describe how these insights into filovirus replication mechanisms and the structure/function characterization of the involved proteins have led to the development of new and innovative antiviral strategies that may help reduce the filovirus disease case fatality rate through post-exposure or prophylactic treatments.
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR7257 CNRS, Parc Scientifique de Luminy, Aix-Marseille Université, Marseille, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Martin
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR7257 CNRS, Parc Scientifique de Luminy, Aix-Marseille Université, Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR7257 CNRS, Parc Scientifique de Luminy, Aix-Marseille Université, Marseille, France. Electronic address: etienne.decroly@afmb.univ-mrs.fr.
authors.forename: Etienne
authors.initials: E
authors.lastname: Decroly
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D055808:Drug Discovery; D029043:Ebolavirus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D016563:Filoviridae / Q000187:drug effects* / Q000502:physiology*; D018702:Filoviridae Infections / Q000188:drug therapy; D029024:Marburgvirus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D014157:Transcription Factors; C479897:VP30 protein, ebola virus; C080980:VP35 protein, filovirus; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Antiviral therapy; Ebola virus; Filovirus; Marburg virus; Mononegavirales