title: Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication.
abstract: Compounds currently used for the treatment of HIV-1 Infections are targeted to viral proteins. However, the high intrinsic mutation and replication rates of HIV-1 often lead to the emergence of drug resistant strains and consequent therapeutic failure. On this basis, cellular cofactors represent attractive new targets for HIV-1 chemotherapy, since targeting a cellular factor that is required for viral replication should help to overcome the problem of viral resistance. We and others have recently reported the identification of compounds suppressing HIV-1 replication by targeting the cellular DEAD-box helicase DDX3. These results provide a proof-of-principle for the feasibility of blocking HIV-1 infection by rendering the host cell environment less favorable for the virus. The rationale for such an approach and its implications in potentially overcoming the problem of drug resistance related to drugs targeting viral proteins will be discussed in the context of the known cellular functions of the DEAD-box helicase DDX3.
authors.affiliation: Institute of Molecular Genetics IGMCNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Garbelli
authors.forename: M
authors.initials: M
authors.lastname: Radi
authors.forename: F
authors.initials: F
authors.lastname: Falchi
authors.forename: S
authors.initials: S
authors.lastname: Beermann
authors.forename: S
authors.initials: S
authors.lastname: Zanoli
authors.forename: F
authors.initials: F
authors.lastname: Manetti
authors.forename: U
authors.initials: U
authors.lastname: Dietrich
authors.forename: M
authors.initials: M
authors.lastname: Botta
authors.forename: G
authors.initials: G
authors.lastname: Maga
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D016415:Sequence Alignment
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases