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Volume 29 Issue 2
April 2014
    Citation: Kuohan Li, Wint Wint Phoo, Dahai Luo. Functional interplay among the flavivirus NS3 protease, helicase, and cofactors .VIROLOGICA SINICA, 2014, 29(2) : 74-85.  http://dx.doi.org/10.1007/s12250-014-3438-6
    shu

    Functional interplay among the flavivirus NS3 protease, helicase, and cofactors

    • Lee Kong Chian School of Medicine, Nanyang Technological University, 61 Biopolis Drive, Proteos Building, #07-03, Singapore 138673, Republic of Singapore

    • Corresponding author: Dahai Luo, luodahai@ntu.edu.sg
    • Received Date: 21 January 2014
      Accepted Date: 19 March 2014
      Published Date: 26 March 2014
      Available online: 01 April 2014
    • Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses (NS2BNS3) form an endoplasmic reticulum (ER) membraneassociated hetero-dimeric complex through the NS2B transmembrane region. The NS2BNS3 complex is multifunctional. The N-terminal region of NS3, and its cofactor NS2B fold into a protease that is responsible for viral polyprotein processing, and the C-terminal domain of NS3 possesses NTPase/RNA helicase activities and is involved in viral RNA replication and virus particle formation. In addition, NS2BNS3 complex has also been shown to modulate viral pathogenesis and the host immune response. Because of the essential functions that the NS2BNS3 complex plays in the flavivirus life cycle, it is an attractive target for antiviral development. This review focuses on the recent biochemical and structural advances of NS2BNS3 and provides a brief update on the current status of drug development targeting this viral protein complex.
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      Functional interplay among the flavivirus NS3 protease, helicase, and cofactors

        Corresponding author: Dahai Luo, luodahai@ntu.edu.sg
      • Lee Kong Chian School of Medicine, Nanyang Technological University, 61 Biopolis Drive, Proteos Building, #07-03, Singapore 138673, Republic of Singapore
      • Received Date: 21 January 2014
      • Accepted Date: 19 March 2014
      • Published Date: 26 March 2014

      Abstract: Flaviviruses are positive-sense RNA viruses, and many are important human pathogens. Nonstructural protein 2B and 3 of the flaviviruses (NS2BNS3) form an endoplasmic reticulum (ER) membraneassociated hetero-dimeric complex through the NS2B transmembrane region. The NS2BNS3 complex is multifunctional. The N-terminal region of NS3, and its cofactor NS2B fold into a protease that is responsible for viral polyprotein processing, and the C-terminal domain of NS3 possesses NTPase/RNA helicase activities and is involved in viral RNA replication and virus particle formation. In addition, NS2BNS3 complex has also been shown to modulate viral pathogenesis and the host immune response. Because of the essential functions that the NS2BNS3 complex plays in the flavivirus life cycle, it is an attractive target for antiviral development. This review focuses on the recent biochemical and structural advances of NS2BNS3 and provides a brief update on the current status of drug development targeting this viral protein complex.

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      MANY FLAVIVIRUSES ARE IMPORTANT HUMAN PATHOGENS