The Transactions of NS3 and NS5 in Flaviviral RNA Replication

Advances in Experimental Medicine and Biology
Moon Y F Tay, Subhash G Vasudevan

Abstract

Dengue virus (DENV) replication occurs in virus-induced vesicles that contain the replication complex (RC) where viral RNA, viral proteins and host proteins participate in RNA-RNA, RNA-protein and protein-protein interactions to ensure viral genome synthesis. However, the details of the multitude of interactions involved in the biogenesis of the infectious virion are not fully understood. In this review, we will focus on the interaction between non-structural (NS) proteins NS3 and NS5, as well as their interactions with viral RNA and briefly also the interaction of NS5 with the host nuclear transport receptor protein importin-α. The multifunctional NS3 protease/helicase and NS5 methyltransferase (MTase)/RNA-dependent RNA polymerase (RdRp) contain all the enzymatic activities required to synthesize the viral RNA genome. The success stories of drug discovery and development with Hepatitis C virus (HCV), a member of the Flaviviridae family, has led to the view that DENV NS3 and NS5 may be attractive antiviral drug targets. However, more than 10 years of intensive research effort by Novatis has revealed that they are not "low hanging fruits" and therefore, the search for potent directly acting antivirals (DAAs) remains a pipeline g...Continue Reading

Citations

Mar 10, 2020·PLoS Neglected Tropical Diseases·Yun WuXun Zhu
Nov 23, 2018·International Journal of Molecular Sciences·Ali MunawarSergei V Strelkov
Feb 23, 2020·Journal of Proteome Research·Shayli Varasteh MoradiKirill Alexandrov
Oct 26, 2021·Food and Environmental Virology·Bibhudutta Mishra, Raviprasad Aduri

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