RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution

Venkataraman, Sangita; Burra, Prasad; Selvarajan, R.

doi:10.3390/v10020076

Cited by 322 publications

(321 citation statements)

References 126 publications

(418 reference statements)

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“…Both of these factors may be important for considering the ability of a virus to evade the immune system, evolve resistance to antivirals, or emerge into a new host species. Improvements in the measurement of mutation rates will enhance our ability to understand mechanisms of fidelity and build on a strong foundation of structural studies (10)(11)(12).…”

Section: Future Directionsmentioning

confidence: 99%

“…Specifically, we address how mutation rates are measured and how evolutionary forces shape viral mutation rates over different time scales. For further discussion on other aspects of viral mutation rates, we refer the reader to articles on polymerase structure and function (10)(11)(12), viral mutational fitness effects (13)(14)(15)(16), evolutionary rates (2-4, 8, 17), and genome evolution (7,18).…”

mentioning

confidence: 99%

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Complexities of Viral Mutation Rates

Peck

Lauring

2018

J Virol

362

314

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Section: Future Directionsmentioning

confidence: 99%

mentioning

confidence: 99%

Complexities of Viral Mutation Rates

Peck

Lauring

2018

J Virol

362

314

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“…Viral polymerases share seven highly conserved motifs that are essentially involved in the nucleotide-binding and catalysis of RNA replication. They are huge, complex structures, which act in association with several non-structural proteins [33].…”

Section: Rna-dependent Rna Polymerasementioning

confidence: 99%

Molecular Investigation of SARS–CoV-2 Proteins and Their Interactions with Antiviral Drugs

Calligari

Bobone

Ricci

et al. 2020

Viruses

110

108

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A new Coronavirus strain, named SARS-CoV-2, suddenly emerged in early December 2019. SARS-CoV-2 resulted in being dramatically infectious, with thousands of people infected. In this scenario, and without effective vaccines available, the importance of an immediate tool to support patients and against viral diffusion becomes evident. In this study, we exploit the molecular docking approach to analyze the affinity between different viral proteins and several inhibitors, originally developed for other viral infections. Our data show that, in some cases, a relevant binding can be detected. These findings support the hypothesis to develop new antiviral agents against COVID-19, on the basis of already established therapies.

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“…S1). This is potentially significant because previous studies have found conserved functional characteristics between the positional homologs of the other nonstructural proteins (20, 21, 23, 46, 61–64), and functional homology between EV 2AB and human norovirus (HuNoV) GII.4 NS1-2 (20, 23). Additionally, when performing multiple sequence alignments of other calicivirus NS1-2s, we found that the C-terminal domain (CTD) of this protein is highly conserved (Fig.…”

Section: Resultsmentioning

confidence: 99%

Recovirus NS1-2 has viroporin activity that induces aberrant cellular calcium signaling to facilitate virus replication

Strtak

Perry

Sharp

et al. 2019

Preprint

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27Enteric viruses in the Caliciviridae family cause acute gastroenteritis in humans and animals, but 28 the cellular processes needed for virus replication and disease remain unknown. A common 29 strategy among enteric viruses, including rotaviruses and enteroviruses, is to encode a viral ion 30 channel (i.e., viroporin) that is targeted to the endoplasmic reticulum (ER) and disrupts host 31 calcium (Ca 2+ ) homeostasis. Previous reports have demonstrated genetic and functional 32 similarities between the nonstructural proteins of caliciviruses and enteroviruses, including the 33 calicivirus NS1-2 protein and the 2B viroporin of enteroviruses. However, it is unknown whether 34 caliciviruses alter Ca 2+ homeostasis for virus replication or whether the NS1-2 protein has 35 viroporin activity like its enterovirus counterpart. To address these questions, we used Tulane 36 virus (TV), a rhesus enteric calicivirus, to examine Ca 2+ signaling during infection and determine 37 whether NS1-2 has viroporin activity that disrupts Ca 2+ homeostasis. We found that TV disrupts 38 increases Ca 2+ signaling during infection and increased cytoplasmic Ca 2+ levels is important for 39 efficient replication. Further, TV NS1-2 localizes to the endoplasmic reticulum (ER), the 40 predominant intracellular Ca 2+ store and the NS2 region has characteristics of a viroporin domain 41 (VPD). NS1-2 had viroporin activity in a classic bacterial functional assay and caused aberrant 42 Ca 2+ signaling when expressed in mammalian cells, but truncation of the VPD abrogated these 43 functions. Together, our data provide new mechanistic insights into the function of the NS2 44 region of NS1-2 and show that like many other enteric viruses, enteric caliciviruses also exploit 45 host Ca 2+ signaling to facilitate their replication. 46 Importance 47Tulane virus is one of many enteric caliciviruses that cause acute gastroenteritis and diarrheal 48 disease. Globally, enteric caliciviruses affect both humans and animals and result in >65 billion 49 dollars per year in treatment and healthcare-associated costs, thus imposing an enormous 50 economic burden. Recent progress has resulted in several cultivation systems (B cell, enteroid 51 and zebrafish larvae) to study human noroviruses, but mechanistic insights into the viral factors 52 and host pathways important for enteric calicivirus replication and infection are largely still 53 lacking. Here we used Tulane virus, a calicivirus that is biologically similar to human 54 noroviruses and can be cultivated in conventional cell culture, to identify and functionally 55 validate NS1-2 as an enteric calicivirus viroporin. Viroporin-mediated calcium signaling may be 56 a broadly utilized pathway for enteric virus replication, and its existence within caliciviruses 57 provides a novel approach to developing antivirals and comprehensive therapeutics for enteric 58 calicivirus diarrheal disease outbreaks. 59 60 61The Caliciviridae family consists of small, non-enveloped single-stranded RNA viruses 62 with five ...

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RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution

Cited by 322 publications

References 126 publications

Complexities of Viral Mutation Rates

Complexities of Viral Mutation Rates

Molecular Investigation of SARS–CoV-2 Proteins and Their Interactions with Antiviral Drugs

Recovirus NS1-2 has viroporin activity that induces aberrant cellular calcium signaling to facilitate virus replication

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