title: Development of Potent Antiviral Drugs Inspired by Viral Hexameric DNA-Packaging Motors with Revolving Mechanism.
abstract: The intracellular parasitic nature of viruses and the emergence of antiviral drug resistance necessitate the development of new potent antiviral drugs. Recently, a method for developing potent inhibitory drugs by targeting biological machines with high stoichiometry and a sequential-action mechanism was described. Inspired by this finding, we reviewed the development of antiviral drugs targeting viral DNA-packaging motors. Inhibiting multisubunit targets with sequential actions resembles breaking one bulb in a series of Christmas lights, which turns off the entire string. Indeed, studies on viral DNA packaging might lead to the development of new antiviral drugs. Recent elucidation of the mechanism of the viral double-stranded DNA (dsDNA)-packaging motor with sequential one-way revolving motion will promote the development of potent antiviral drugs with high specificity and efficiency. Traditionally, biomotors have been classified into two categories: linear and rotation motors. Recently discovered was a third type of biomotor, including the viral DNA-packaging motor, beside the bacterial DNA translocases, that uses a revolving mechanism without rotation. By analogy, rotation resembles the Earth's rotation on its own axis, while revolving resembles the Earth's revolving around the Sun (see animations at http://rnanano.osu.edu/movie.html). Herein, we review the structures of viral dsDNA-packaging motors, the stoichiometries of motor components, and the motion mechanisms of the motors. All viral dsDNA-packaging motors, including those of dsDNA/dsRNA bacteriophages, adenoviruses, poxviruses, herpesviruses, mimiviruses, megaviruses, pandoraviruses, and pithoviruses, contain a high-stoichiometry machine composed of multiple components that work cooperatively and sequentially. Thus, it is an ideal target for potent drug development based on the power function of the stoichiometries of target complexes that work sequentially.
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Department of Physiology and Cell Biology, College of Medicine, and the Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Pi
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Department of Physiology and Cell Biology, College of Medicine, and the Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Zhengyi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, Canterbury, New Zealand.
authors.forename: Venkata
authors.initials: V
authors.lastname: Chelikani
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yoder
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Department of Physiology and Cell Biology, College of Medicine, and the Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Mamuka
authors.initials: M
authors.lastname: Kvaratskhelia
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Department of Physiology and Cell Biology, College of Medicine, and the Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA guo.1091@osu.edu.
authors.forename: Peixuan
authors.initials: P
authors.lastname: Guo
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D042003:DNA Packaging / Q000187:drug effects*; D004267:DNA Viruses / Q000187:drug effects / Q000201:enzymology; D055808:Drug Discovery; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D019065:Virus Assembly / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D020409:Molecular Motor Proteins; D014764:Viral Proteins