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.
Keywords: Antiviral therapy, cancer, DEAD-box, drug design, HIV-1, RNA helicase, viral replication, viral proteins, HIV-1 chemotherapy, DDX3
Current Medicinal Chemistry
Title: Targeting the Human DEAD-Box Polypeptide 3 (DDX3) RNA Helicase as a Novel Strategy to Inhibit Viral Replication
Volume: 18 Issue: 20
Author(s): A. Garbelli, M. Radi, F. Falchi, S. Beermann, S. Zanoli, F. Manetti, U. Dietrich, M. Botta and G. Maga
Affiliation:
Keywords: Antiviral therapy, cancer, DEAD-box, drug design, HIV-1, RNA helicase, viral replication, viral proteins, HIV-1 chemotherapy, DDX3
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.
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Garbelli A., Radi M., Falchi F., Beermann S., Zanoli S., Manetti F., Dietrich U., Botta M. and Maga G., Targeting the Human DEAD-Box Polypeptide 3 (DDX3) RNA Helicase as a Novel Strategy to Inhibit Viral Replication, Current Medicinal Chemistry 2011; 18 (20) . https://dx.doi.org/10.2174/092986711796391688
DOI https://dx.doi.org/10.2174/092986711796391688 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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