Norovirus RNA‐dependent RNA polymerase: A computational study of metal‐binding preferences

Shaik, Munan; Bhattacharjee, Nicholus; Feliks, Mikołaj; Ng, Kenneth; Field, Martin J.

doi:10.1002/prot.25304

Cited by 13 publications

(11 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 ). No amino acid change was observed within the active site cleft [ 39 – 41 ], and only 5 residues had medium to low conserved physico-chemical properties (5 ≥ Score) [ 42 ]. However, in vivo studies would be required to determine whether these amino acid variations have any effect on the polymerase activity.…”

Section: Resultsmentioning

confidence: 99%

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Petronella

Ronholm

Suresh³

et al. 2018

BMC Infect Dis

View full text Add to dashboard Cite

BackgroundHuman norovirus is the leading cause of viral gastroenteritis globally, and the GII.4 has been the most predominant genotype for decades. This genotype has numerous variants that have caused repeated epidemics worldwide. However, the molecular evolutionary signatures among the GII.4 variants have not been elucidated throughout the viral genome.MethodA metagenomic, next-generation sequencing method, based on Illumina RNA-Seq, was applied to determine norovirus sequences from clinical samples.ResultsHerein, the obtained deep-sequencing data was employed to analyze full-genomic sequences from GII.4 variants prevailing in Canada from 2012 to 2016. Phylogenetic analysis demonstrated that the majority of these sequences belong to New Orleans 2009 and Sydney 2012 strains, and a recombinant sequence was also identified. Genome-wide similarity analyses implied that while the capsid gene is highly diverse among the isolates, the viral protease and polymerase genes remain relatively conserved. Numerous amino acid substitutions were observed at each putative antigenic epitope of the VP1 protein, whereas few amino acid changes were identified in the polymerase protein. Co-infection with other enteric RNA viruses was investigated and the astrovirus genome was identified in one of the samples.ConclusionsOverall this study demonstrated the application of whole genome sequencing as an important tool in molecular characterization of noroviruses.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3419-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Petronella

Ronholm

Suresh³

et al. 2018

BMC Infect Dis

View full text Add to dashboard Cite

show abstract

“…Structures of well-studied RdRPs, including hepatitis C virus RdRP (PDB ID: 4WTA ( 56 )) and severe acute respiratory syndrome coronavirus 2 RdRP (PDB ID: 72CK ( 57 )) ( Fig. 9 , C and D ; see also PDB ID: 2E9T ( 58 ), PDB ID: 5TSN ( 59 ), and PDB ID: 1S48 ( 60 )), show a putative TS pocket composed of an RT0 loop cognate (termed motif G in RdRPs) and the fingertips loop on either side ( 61 ). The TS pocket homology between RdRPs and group II intron RTs suggests a common mechanism for binding the acceptor RNA template.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for template switching by a group II intron–encoded non-LTR-retroelement reverse transcriptase

Lentzsch

Stamos

Yao

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

Reverse transcriptases (RTs) can switch template strands during complementary DNA synthesis, enabling them to join discontinuous nucleic acid sequences. Template switching (TS) plays crucial roles in retroviral replication and recombination, is used for adapter addition in RNA-Seq, and may contribute to retroelement fitness by increasing evolutionary diversity and enabling continuous complementary DNA synthesis on damaged templates. Here, we determined an X-ray crystal structure of a TS complex of a group II intron RT bound simultaneously to an acceptor RNA and donor RNA template–DNA primer heteroduplex with a 1-nt 3′-DNA overhang. The structure showed that the 3′ end of the acceptor RNA binds in a pocket formed by an N-terminal extension present in non–long terminal repeat–retroelement RTs and the RT fingertips loop, with the 3′ nucleotide of the acceptor base paired to the 1-nt 3′-DNA overhang and its penultimate nucleotide base paired to the incoming dNTP at the RT active site. Analysis of structure-guided mutations identified amino acids that contribute to acceptor RNA binding and a phenylalanine residue near the RT active site that mediates nontemplated nucleotide addition. Mutation of the latter residue decreased multiple sequential template switches in RNA-Seq. Our results provide new insights into the mechanisms of TS and nontemplated nucleotide addition by RTs, suggest how these reactions could be improved for RNA-Seq, and reveal common structural features for TS by non–long terminal repeat–retroelement RTs and viral RNA–dependent RNA polymerases.

show abstract

“…Consistently, Cu inhibits influenza virus replication by blocking the activity of RdRP or damaging its negative-sense RNA [ 84 , 92 ]. Computational studies have also depicted that RdRP of norovirus can accept Cu with the highest binding energy compared to other metal ions [93] . Second, Cu may exploit the mechanism of redox signaling by generating ROS, which can destroy the virus.…”

Section: The Molecular Basis Of Copper (Cu) In Biological Systemsmentioning

confidence: 98%

Potential molecular mechanisms of zinc- and copper-mediated antiviral activity on COVID-19

et al. 2021

View full text Add to dashboard Cite

Novel coronavirus disease 2019 (COVID-19) has spread across the globe; and surprisingly, no potentially protective or therapeutic antiviral molecules are available to treat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, zinc (Zn) and copper (Cu) have been shown to exert protective effects due to their antioxidant, anti-inflammatory and antiviral properties. Therefore, it is hypothesized that supplementation with Zn and Cu alone or as an adjuvant may be beneficial with promising efficacy and a favorable safety profile to mitigate symptoms, as well as halt progression of the severe form of SARS-CoV-2 infection. The objective of this review is to discuss the proposed underlying molecular mechanisms and their implications for combating SARS-CoV-2 infection in response to Zn and Cu administration. Several clinical trials have also included the use of Zn as an adjuvant therapy with dietary regimens/antiviral drugs against COVID-19 infection. Overall, this review summarizes that nutritional intervention with Zn and Cu may offer an alternative treatment strategy by eliciting their virucidal effects through several fundamental molecular cascades, such as, modulation of immune responses, redox signaling, autophagy, and obstruction of viral entry and genome replication during SARS-CoV-2 infection.

show abstract

Norovirus RNA‐dependent RNA polymerase: A computational study of metal‐binding preferences

Cited by 13 publications

References 75 publications

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Structural basis for template switching by a group II intron–encoded non-LTR-retroelement reverse transcriptase

Potential molecular mechanisms of zinc- and copper-mediated antiviral activity on COVID-19

Contact Info

Product

Resources

About