The Spring α-Helix Coordinates Multiple Modes of HCV (Hepatitis C Virus) NS3 Helicase Action

Gu, Meigang; Rice, Charles M.

doi:10.1074/jbc.m115.704379

Cited by 16 publications

(21 citation statements)

References 47 publications

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“…The NS3 protease domain is responsible for HCV polyprotein processing and also contributes to the activity of the helicase domain through an allosteric mechanism [ 115 , 116 , 117 ]. Specific mutations in the NS3 helicase domain modulating the nucleic acid unwinding activity, which also affect HCV’s replicative ability, indicate a role of NS3h in HCV RNA synthesis [ 118 , 119 , 120 ]. The NS3h may play roles in (i) resolving strong stem-loop structures at the 3’ end of the genome to facilitate initiation of RNA synthesis by NS5B; (ii) unwinding replication intermediates (i.e., dsRNA) during RNA synthesis to support NS5B in the elongation phase; and (iii) striping proteins off the RNA or delivering RNA for packaging into virions via the process of ssRNA translocation [ 105 , 121 ].…”

Section: Genome Replicationmentioning

confidence: 99%

Hepatitis C Viral Replication Complex

Yang

2021

Viruses

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The life cycle of the hepatitis C virus (HCV) can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and release. HCV genomic RNA replication occurs in the replication organelles (RO) and is tightly linked to ER membrane alterations containing replication complexes (proteins NS3 to NS5B). The amplification of HCV genomic RNA could be regulated by the RO biogenesis, the viral RNA structure (i.e., cis-acting replication elements), and both viral and cellular proteins. Studies on HCV replication have led to the development of direct-acting antivirals (DAAs) targeting the replication complex. This review article summarizes the viral and cellular factors involved in regulating HCV genomic RNA replication and the DAAs that inhibit HCV replication.

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Section: Genome Replicationmentioning

confidence: 99%

Hepatitis C Viral Replication Complex

Yang

2021

Viruses

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“…Virus-encoded ATPase-driven helicases have been identified in numerous human pathogens. Helicases from several (+)RNA viruses have been characterized, including NS3 helicases from flaviviruses such as dengue virus, HCV, West Nile virus, yellow fever virus, and Japanese encephalitis virus (Cao et al, 2016;Gu and Rice, 2016;Jain et al, 2016;Lin et al, 2017;Nedjadi et al, 2015;Wu et al, 2005). SARS and MERS coronaviruses encode nsp13 with helicase activity (Adedeji and Lazarus, 2016;Hao et al, 2017;Seybert et al, 2000).…”

Section: Helicasesmentioning

confidence: 99%

In vitro methods for testing antiviral drugs

Rumlová

Ruml

2018

Biotechnology Advances

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Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses.

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“…Motif Y contains a tyrosine residue that π−π stacks below the adenine base of the ATP analog. As mentioned above, this motif is hypothesized to transduce ATP binding and hydrolysis events to conformational changes in the nucleic acid substrate within NS3/NPH-II helicases [52,62].…”

Section: Conformational Snapshots Of Hcv Ns3 Through the Use Of Atp Amentioning

confidence: 99%

Structural Basis of DEAH/RHA Helicase Activity

Chen

Ferré-D′Amaré

2017

Crystals

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DEAH/RHA helicases are members of a large group of proteins collectively termed DExH-box, which also include Ski2-like and NS3/NPH-II helicases. By binding and remodeling DNA and RNA, DEAH/RHA helicases play critical roles in many cellular processes ranging from transcription and splicing to ribosome biogenesis, innate immunity and stress granule formation. While numerous crystal structures of other DExH-box proteins helicases have been reported, no structures of DEAH/RHA helicases bound to nucleic acid substrates have been available until the recent co-crystal structures of the maleless (MLE) and Prp43p bound to RNA. This review examines how these new structures provide a starting point to understand how DEAH/RHA helicases bind to, translocate on, and unwind nucleic acid substrates.

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The Spring α-Helix Coordinates Multiple Modes of HCV (Hepatitis C Virus) NS3 Helicase Action

Cited by 16 publications

References 47 publications

Hepatitis C Viral Replication Complex

Hepatitis C Viral Replication Complex

In vitro methods for testing antiviral drugs

Structural Basis of DEAH/RHA Helicase Activity

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