In Silico Derived Small Molecules Bind the Filovirus VP35 Protein and Inhibit Its Polymerase Cofactor Activity

• Published in: Journal of molecular biology Vol. 426; no. 10; pp. 2045 - 2058
• Main Authors: Brown, Craig S., Lee, Michael S., Leung, Daisy W., Wang, Tianjiao, Xu, Wei, Luthra, Priya, Anantpadma, Manu, Shabman, Reed S., Melito, Lisa M., MacMillan, Karen S., Borek, Dominika M., Otwinowski, Zbyszek, Ramanan, Parameshwaran, Stubbs, Alisha J., Peterson, Dayna S., Binning, Jennifer M., Tonelli, Marco, Olson, Mark A., Davey, Robert A., Ready, Joseph M., Basler, Christopher F., Amarasinghe, Gaya K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 15.05.2014
• Subjects: antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; antivirals; Coenzymes - antagonists & inhibitors; Coenzymes - chemistry; Computer Simulation; Crystallography, X-Ray; DNA-Directed RNA Polymerases - antagonists & inhibitors; DNA-Directed RNA Polymerases - metabolism; Ebolavirus; Ebolavirus - drug effects; Ebolavirus - enzymology; enzyme activity; filoviral inhibitors; genome; in silico drug discovery; interferons; messenger RNA; Models, Molecular; mutation; nuclear magnetic resonance spectroscopy; Nuclear Magnetic Resonance, Biomolecular; nucleoproteins; pathogenesis; polypeptides; Protein Binding; Protein Interaction Domains and Motifs - physiology; protein-protein interactions; Pyrroles - chemistry; Pyrroles - metabolism; Pyrroles - pharmacology; RNA-directed RNA polymerase; screening; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Viral Regulatory and Accessory Proteins - antagonists & inhibitors; Viral Regulatory and Accessory Proteins - chemistry; virus replication; VP35; X-ray diffraction; filoviral inhibitors; antivirals; NP; EBOV; IID; DMSO; PPI; in silico drug discovery; PDB; IFN; GFP; VP35; MG; MARV; HSQC

The Ebola virus (EBOV) genome only encodes a single viral polypeptide with enzymatic activity, the viral large (L) RNA-dependent RNA polymerase protein. However, currently, there is limited information about the L protein, which has hampered the development of antivirals. Therefore, antifiloviral th...