TAILIEUCHUNG - Báo cáo khoa học: Progress for dengue virus diseases Towards the NS2B–NS3pro inhibition for a therapeutic-based approach

The LolCDE complex ofEscherichia colibelongs to the ATP-binding cas-sette transporter superfamily and mediates the detachment of lipoproteins from the inner membrane, thereby initiating lipoprotein sorting to the outer membrane. The complex is composed of one copy each of membrane subunits LolC and LolE, and two copies of ATPase subunit LolD. | ễFEBS Journal REVIEW ARTICLE Progress for dengue virus diseases Towards the NS2B-NS3pro inhibition for a therapeutic-based approach Sonia Melino and Maurizio Paci Department of ChemicalScience and Technology University of Rome Tor Vergata Italy Keywords dengue hemorrhagic fever dengue virus NS3 protease inhibitors vaccines viral diseases viral serine protease Correspondence S. Melino Dipartimento di Scienze e Tecnologie Chimiche University di Roma Tor Vergata via della Ricerca Scientifica 00133 Rome Italy Fax 39 0672594328 Tel 39 0672594449 E-mail melinos@ Received 22 January 2007 revised 16 March 2007 accepted 17 April 2007 doi Transmitted by the Aedes aegypti mosquito the dengue virus is the etiological agent of dengue fever dengue hemorrhagic fever and dengue shock syndrome and as such is a significant factor in the high death rate found in most tropical and subtropical areas of the world. Dengue diseases are not only a health burden to developing countries but pose an emerging problem worldwide. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators during dengue disease plays a key role in inducing plasma leakage shock and hemorrhagic manifestations. Currently there are no vaccines available against dengue virus although several tetravalent live-attenuated dengue vaccines are in clinical phases I or II and prevention through vaccination has become a major priority on the agendas of the World Health Organization and of national ministries of health and military organizations. An alternative to vaccines is found in therapeutic-based approaches. Understanding the molecular mechanisms of viral replication has led to the development of potential drugs and new molecular viral targets for therapy are emerging. The NS3 protease domain of the NS3 protein is responsible for processing the viral polyprotein and its inhibition .

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