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

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...

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Main Authors: Li, Kuohan, Phoo, Wint Wint, Luo, Dahai
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2014
Subjects:
Online Access:https://hdl.handle.net/10356/80089
http://hdl.handle.net/10220/19288
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author Li, Kuohan
Phoo, Wint Wint
Luo, Dahai
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Li, Kuohan
Phoo, Wint Wint
Luo, Dahai
author_sort Li, Kuohan
collection NTU
description 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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spelling ntu-10356/800892020-11-01T05:11:41Z Functional interplay among the flavivirus NS3 protease, helicase, and cofactors Li, Kuohan Phoo, Wint Wint Luo, Dahai Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Medicine 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. Accepted version 2014-05-02T05:27:20Z 2019-12-06T13:40:30Z 2014-05-02T05:27:20Z 2019-12-06T13:40:30Z 2014 2014 Journal Article Li, K., Phoo, W. W., & Luo, D. (2014). Functional interplay among the flavivirus NS3 protease, helicase, and cofactors. Virologica Sinica, 29(2), 74-85. 1674-0769 https://hdl.handle.net/10356/80089 http://hdl.handle.net/10220/19288 10.1007/s12250-014-3438-6 en Virologica sinica © 2014 WIV, CAS and Springer-Verlag Berlin Heidelberg. This is the author created version of a work that has been peer reviewed and accepted for publication by Virologica Sinica, WIV, CAS and Springer-Verlag Berlin Heidelberg. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1007/s12250-014-3438-6]. 12 p. application/pdf
spellingShingle DRNTU::Science::Medicine
Li, Kuohan
Phoo, Wint Wint
Luo, Dahai
Functional interplay among the flavivirus NS3 protease, helicase, and cofactors
title Functional interplay among the flavivirus NS3 protease, helicase, and cofactors
title_full Functional interplay among the flavivirus NS3 protease, helicase, and cofactors
title_fullStr Functional interplay among the flavivirus NS3 protease, helicase, and cofactors
title_full_unstemmed Functional interplay among the flavivirus NS3 protease, helicase, and cofactors
title_short Functional interplay among the flavivirus NS3 protease, helicase, and cofactors
title_sort functional interplay among the flavivirus ns3 protease helicase and cofactors
topic DRNTU::Science::Medicine
url https://hdl.handle.net/10356/80089
http://hdl.handle.net/10220/19288
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