The minimalist architectures of viroporins and their therapeutic implications.
Many viral genomes encode small, integral membrane proteins that form homo-oligomeric channels in membrane, and they transport protons, cations, and other molecules across the membrane barrier to aid various steps of viral entry and maturation. These viral proteins, collectively named viroporins, are crucial for viral pathogenicity. In the past five years, structures obtained by nuclear magnetic resonance (NMR), X-ray crystallography, and electron microscopy (EM) showed that viroporins often adopt minimalist architectures to achieve their functions. A number of small molecules have been identified to interfere with their channel activities and thereby inhibit viral infection, making viroporins potential drug targets for therapeutic intervention. The known architectures and inhibition mechanisms of viroporins differ significantly from each other, but some common principles are shared between them. This review article summarizes the recent developments in the structural investigation of viroporins and their inhibition by antiviral compounds. This article is part of a Special Issue entitled: Viral Membrane Proteins-Channels for Cellular Networking.
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
Bo
B
OuYang
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; National Center for Protein Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: james_chou@hms.harvard.edu.
James J
JJ
Chou
D000547:Amantadine / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*
D000998:Antiviral Agents; D014763:Viral Matrix Proteins; D000547:Amantadine
Hepatitis C; Influenza; M2; Structure; Viroporin; p7