Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronavirus genome replication and transcription take place at cytoplasmic membranes and involve coordinated processes of both continuous and discontinuous RNA synthesis that are mediated by the viral replicase, a huge protein complex encoded by the 20-kb replicase gene. The replicase complex is believed to be comprised of up to 16 viral subunits and a number of cellular proteins. Besides RNA-dependent RNA polymerase, RNA helicase, and protease activities, which are common to RNA viruses, the coronavirus replicase was recently predicted to employ a variety of RNA processing enzymes that are not (or extremely rarely) found in other RNA viruses and include putative sequence-specific endoribonuclease, 3'-to-5' exoribonuclease, 2'-O-ribose methyltransferase, ADP ribose 1"-phosphatase and, in a subset of group 2 coronaviruses, cyclic phosphodiesterase activities. This chapter reviews (1) the organization of the coronavirus replicase gene, (2) the proteolytic processing of the replicase by viral proteases, (3) the available functional and structural information on individual subunits of the replicase, such as proteases, RNA helicase, and the RNA-dependent RNA polymerase, and (4) the subcellular localization of coronavirus proteins involved in RNA synthesis. Although many molecular details of the coronavirus life cycle remain to be investigated, the available information suggests that these viruses and their distant nidovirus relatives employ a unique collection of enzymatic activities and other protein functions to synthesize a set of 5'-leader-containing subgenomic mRNAs and to replicate the largest RNA virus genomes currently known.
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PMID:The coronavirus replicase. 1560 9

As the largest RNA virus, coronavirus replication employs complex mechanisms and involves various viral and cellular proteins. The first open reading frame of the coronavirus genome encodes a large polyprotein, which is processed into a number of viral proteins required for viral replication directly or indirectly. These proteins include the RNA-dependent RNA polymerase (RdRp), RNA helicase, proteases, metal-binding proteins, and a number of other proteins of unknown function. Genetic studies suggest that most of these proteins are involved in viral RNA replication. In addition to viral proteins, several cellular proteins, such as heterogeneous nuclear ribonucleoprotein (hnRNP) A1, polypyrimidine-tract-binding (PTB) protein, poly(A)-binding protein (PABP), and mitochondrial aconitase (m-aconitase), have been identified to interact with the critical cis-acting elements of coronavirus replication. Like many other RNA viruses, coronavirus may subvert these cellular proteins from cellular RNA processing or translation machineries to play a role in viral replication.
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PMID:Viral and cellular proteins involved in coronavirus replication. 1560 10

The complete nucleotide sequence of a novel member of the genus Crinivirus (family Closteroviridae), isolated from blackberry and tentatively named Blackberry yellow vein associated virus, was determined. The virus possesses a bipartite genome. RNA 1 is 7,801 nucleotides in length and papain-like protease, methyltransferase, RNA helicase and RNA-dependent RNA polymerase motifs have been identified in the proteins coded for by this molecule. The polymerase is probably expressed via a +1 ribosomal frameshift, a common feature among members of the Closteroviridae. RNA 2 is 7,917 nucleotides long and encodes nine open reading frames, similar in size and position to orthologous genes of other criniviruses with the exception of a second hydrophobic peptide found near the 5' terminus of the molecule. Phylogenetic analysis revealed a close relationship between Blackberry yellow vein associated virus and Beet pseudo yellows virus, another crinivirus that infects small fruit crops.
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PMID:Nucleotide sequence of Blackberry yellow vein associated virus, a novel member of the Closteroviridae. 1633 99

The complete nucleotide sequence of the genomic RNA of a marine fungoid protist-infecting virus (Schizochytrium single-stranded RNA virus; SssRNAV) has been determined. The viral RNA is single-stranded with a positive sense and is 9,018 nt in length [excluding the 3' poly(A) tail]. It contains two long open reading frames (ORFs), which are separated by an intergenic region of 92 nt. The 5' ORF (ORF1) is preceded by an untranslated leader sequence of 554 nt. The 3' large ORF (ORF2) and an additional ORF (ORF3) overlap ORF2 by 431 nt and are followed by an untranslated region of 70 nt [excluding the 3' poly(A) tail]. The deduced amino acid sequences of ORF1 and ORF2 products show similarity to non-structural and structural proteins of dicistroviruses, respectively. However, Northern blot analysis suggests that SssRNAV synthesizes subgenomic RNAs to translate ORF2 and ORF3, showing that the translation mechanism of downstream ORFs is distinct from that of dicistroviruses. Furthermore, although considerable similarities were detected by using a blast genome database search, phylogenetic analysis based on both the nucleotide and amino acid sequences of the putative RNA-dependent RNA polymerase (RdRp) and the RNA helicase suggests that SssRNAV is phylogenetically distinct from other virus families. Therefore, it is concluded that SssRNAV is not a member of any currently defined virus family and belongs to a novel, unrecognized virus group.
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PMID:Complete nucleotide sequence and genome organization of a single-stranded RNA virus infecting the marine fungoid protist Schizochytrium sp. 1647 96

Deformed wing virus (DWV) of honeybees (Apis mellifera) is closely associated with characteristic wing deformities, abdominal bloating, paralysis, and rapid mortality of emerging adult bees. The virus was purified from diseased insects, and its genome was cloned and sequenced. The genomic RNA of DWV is 10,140 nucleotides in length and contains a single large open reading frame encoding a 328-kDa polyprotein. The coding sequence is flanked by a 1,144-nucleotide 5' nontranslated leader sequence and a 317-nucleotide 3' nontranslated region, followed by a poly(A) tail. The three major structural proteins, VP1 (44 kDa), VP2 (32 kDa), and VP3 (28 kDa), were identified, and their genes were mapped to the N-terminal section of the polyprotein. The C-terminal part of the polyprotein contains sequence motifs typical of well-characterized picornavirus nonstructural proteins: an RNA helicase, a chymotrypsin-like 3C protease, and an RNA-dependent RNA polymerase. The genome organization, capsid morphology, and sequence comparison data indicate that DWV is a member of the recently established genus Iflavirus.
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PMID:Molecular and biological characterization of deformed wing virus of honeybees (Apis mellifera L.). 1664 Dec 91

Coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. The interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. The outbreak of severe acute respiratory syndrome (SARS) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals. In this study, we sampled bat populations in 15 provinces of China and reveal that approximately 6.5% of the bats, from diverse species distributed throughout the region, harbor coronaviruses. Full genomes of four coronavirues from bats were sequenced and analyzed. Phylogenetic analyses of the spike, envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, revealed that bat coronaviruses cluster in three different groups: group 1, another group that includes all SARS and SARS-like coronaviruses (putative group 4), and an independent bat coronavirus group (putative group 5). Further genetic analyses showed that different species of bats maintain coronaviruses from different groups and that a single bat species from different geographic locations supports similar coronaviruses. Thus, the findings of this study suggest that bats may play an integral role in the ecology and evolution of coronaviruses.
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PMID:Prevalence and genetic diversity of coronaviruses in bats from China. 1684 Mar 28

Recently, nitric oxide (NO) has been shown to suppress dengue virus (DENV) RNA and protein accumulation in infected cells. In this report, the potential target of the inhibitory effect of NO was studied at the molecular level. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), showed an inhibitory effect on RNA accumulation at around 8-14 h post-infection, which corresponded to the step of viral RNA synthesis in the DENV life cycle. The activity of the viral replicase isolated from SNAP-treated DENV-2-infected cells was suppressed significantly compared with that of the negative-control N-acetyl-DL-penicillamine (NAP)-treated cells. Further investigations on the molecular target of NO action showed that the activity of recombinant DENV-2 NS5 in negative-strand RNA synthesis was affected in the presence of 5 mM SNAP in in vitro RNA-dependent RNA polymerase (RdRp) assays, whereas the RNA helicase activity of DENV-2 NS3 was not inhibited up to a concentration of 15 mM SNAP. These results suggest that the inhibitory effect of NO on DENV infection is partly via inhibition of the RdRp activity, which then downregulates viral RNA synthesis.
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PMID:Antiviral action of nitric oxide on dengue virus type 2 replication. 1696 59

Dengue viruses (DENV) have 5'-capped RNA genomes of (+) polarity and encode a single polyprotein precursor that is processed into mature viral proteins. NS2B, NS3 and NS5 proteins catalyse/activate enzyme activities that are required for key processes in the virus life cycle. The heterodimeric NS2B/NS3 is a serine protease required for processing. Using a high-throughput protease assay, we screened a small molecule chemical library and identified -200 compounds having > or = 50% inhibition. Moreover, NS3 exhibits RNA-stimulated NTPase, RNA helicase and the 5'-RNA triphosphatase activities. The NTPase and the 5'-RTPase activities of NS3 are stimulated by interaction with NS5. Moreover, the conserved, positively charged motif in DENV-2 NS3, 184RKRK, is required for RNA binding and modulates the RNA-dependent enzyme activities of NS3. To study viral replication, a variety of methods are used such as the in vitro RNA-dependent RNA polymerase assays that utilize lysates from DENV-2-infected mosquito or mammalian cells or the purified NS5 along with exogenous short subgenomic viral RNAs or the replicative intracellular membrane-bound viral RNAs as templates. In addition, a cell-based DENV-2 replicon RNA encoding a luciferase reporter is also used to examine the role of cis-acting elements within the 3' UTR and the RKRK motif in viral replication.
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PMID:Multiple enzyme activities of flavivirus proteins. 1731 55

Since an outbreak of severe acute respiratory syndrome (SARS) was averted in 2004, many novel coronaviruses have been recognized from different species, including humans. Bats have provided the most diverse assemblages of coronaviruses, suggesting that they may be the natural reservoir. Continued virological surveillance has proven to be the best way to avert this infectious disease at the source. Here we provide the first description of a previously unidentified coronavirus lineage detected from wild Asian leopard cats (Prionailurus bengalensis) and Chinese ferret badgers (Melogale moschata) during virological surveillance in southern China. Partial genome analysis revealed a typical coronavirus genome but with a unique putative accessory gene organization. Phylogenetic analyses revealed that the envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, of these novel coronaviruses were most closely related to those of group 3 coronaviruses identified from birds, while the spike protein gene was most closely related to that of group 1 coronaviruses from mammals. However, these viruses always fell into an outgroup phylogenetic relationship with respect to other coronaviruses and had low amino acid similarity to all known coronavirus groups, indicating that they diverged early in the evolutionary history of coronaviruses. These results suggest that these viruses may represent a previously unrecognized evolutionary pathway, or possibly an unidentified coronavirus group. This study demonstrates the importance of systematic virological surveillance in market animals for understanding the evolution and emergence of viruses with infectious potential.
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PMID:Detection of a novel and highly divergent coronavirus from asian leopard cats and Chinese ferret badgers in Southern China. 1745 38

Four novel series of base modified ribonucleoside analogues were synthesized and evaluated as potential anti-HCV agents. For two compounds notable anti-HCV activity was observed The triphosphates of bicyclic pyrimidine ribonucleosides were studied as substrates/inhibitors of HCV RNA-dependent RNA polymerase (RdRp, NS5B protein) and RNA helicase/NTPase (NS3 protein).
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PMID:Base-modified ribonucleosides as potential anti-hepatitis C virus agents. 1877 32


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