Virologica Sinica

, Volume 29, Issue 2, pp 74–85 | Cite as

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

  • Kuohan Li
  • Wint Wint Phoo
  • Dahai LuoEmail author


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) membrane-associated 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.


crystal structures antiviral drug target serine protease RNA helicase 


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Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeRepublic of Singapore

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