title: The RNA capping machinery as an anti-infective target.
abstract: A number of different human pathogens code for their own enzymes involved in the synthesis of the RNA cap structure. Although the RNA cap structures originating from human and microbial enzymes are often identical, the subunit composition, structure and catalytic mechanisms of the microbial-encoded enzymes involved in the synthesis of the RNA cap structure are often significantly different from those of host cells. As a consequence, these pathogenic cap-forming enzymes are potential targets for antimicrobial drugs. During the past few years, experimental studies have started to demonstrate that inhibition of the RNA capping activity is a reasonable approach for the development of antimicrobial agents. The combination of structural, biochemical, and molecular modeling studies are starting to reveal novel molecules that can serve as starting blocks for the design of more potent and specific antimicrobial agents. Here, we examine various strategies that have been developed to inhibit microbial enzymes involved in the synthesis of the RNA cap structure, emphasizing the challenges remaining to design potent and selective drugs.
authors.affiliation: Département de Biochimie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors.forename: Moheshwarnath
authors.initials: M
authors.lastname: Issur
authors.forename: Frédéric
authors.initials: F
authors.lastname: Picard-Jean
authors.forename: Martin
authors.initials: M
authors.lastname: Bisaillon
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D058990:Molecular Targeted Therapy / Q000379:methods*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010710:Phosphates / Q000138:chemical synthesis / Q000737:chemistry; D012314:RNA Cap Analogs / Q000138:chemical synthesis / Q000737:chemistry; D012315:RNA Caps / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014638:Vanadates / Q000138:chemical synthesis / Q000737:chemistry; D000098556:mRNA Guanylyltransferases
chemical_list: D000890:Anti-Infective Agents; D010710:Phosphates; D012314:RNA Cap Analogs; D012315:RNA Caps; D014638:Vanadates; D009713:Nucleotidyltransferases; D000098556:mRNA Guanylyltransferases