Coronaviruses post-SARS: update on replication and pathogenesis

Perlman, Stanley; Netland, Jason

doi:10.1038/nrmicro2147

Cited by 1,567 publications

(1,699 citation statements)

References 142 publications

(170 reference statements)

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“…Among these are the proteolytic activities endowed by nsp3 and nsp5, required to mature pp1a and pp1ab polyproteins into individual non-structural proteins (11,12); the RNA-dependent RNA polymerase by nsp12, and a putative RNA primase, nsp8, involved in replication and transcription (13)(14)(15); several RNA modification enzymes, such as nsp14, an exoribonuclease, nsp15, an endoribonuclease, and nsp13, a helicase/RNA triphosphatase (16,17); and two S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases carried by nsp14 (N7-MTase) and nsp16 (2ЈO-MTase) (18 -20). In addition, some of these nsps have thus far no known function nor enzymatic activity, and/or their functions remain more elusive (nsp1, nsp2, nsp4, nsp6, nsp9, nsp10, and nsp11), even if some of them may regulate host cellular functions (nsp1, nsp4, and nsp6) or enzymatic activities from the replication-transcription complex (10).…”

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confidence: 99%

Molecular Mapping of the RNA Cap 2′-O-Methyltransferase Activation Interface between Severe Acute Respiratory Syndrome Coronavirus nsp10 and nsp16*

Lugari

Betzi

Decroly

et al. 2010

Journal of Biological Chemistry

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Several protein-protein interactions within the SARS-CoV proteome have been identified, one of them being between nonstructural proteins nsp10 and nsp16. In this work, we have mapped key residues on the nsp10 surface involved in this interaction. Alanine-scanning mutagenesis, bioinformatics, and molecular modeling were used to identify several "hot spots," such as Val 42 Coronaviruses (CoVs),7 classified into the family Coronaviridae in the order Nidovirales, possess a viral RNA genome that is among the largest known (2). They include important pathogens of livestock, wild and companion animals, and humans, such as the severe acute respiratory syndrome CoV (SARSCoV) (3-5). They are mainly etiological agents of respiratory and enteric diseases, exemplified by the worldwide pandemic of SARS-CoV spreading in 2003 from Asia, with a final number of cases around 8,000 and a 10% mortality.The genome of SARS-CoV contains a single-stranded plussense RNA of ϳ29.7 kb (2). At the molecular level, CoVs employ a variety of unusual strategies to accomplish a complex program of gene expression (5). Coronavirus replication requires the synthesis of both genomic and multiple subgenomic RNA species and the assembly of progeny virions by a pathway that is unique among enveloped RNA viruses (5-7). Fourteen open reading frames (ORFs) have been identified, of which 12 are located in the 3Ј-end of the genome. The other two ORFs (1a and 1b), which are located in the 5Ј-proximal twothirds of the genome, encode two large polyproteins translated directly from genomic RNA. ORF 1b is expressed by a Ϫ1 ribosomal frameshifting at the end of pp1a, extending its coding sequence and thus generating the pp1ab polyprotein (6). These two polyproteins are cleaved into 16 functional viral replicase proteins called nsp1 to -16 (for non-structural proteins 1-16). Those nsps form the membrane-bound replication-transcription complex, which is localized to a network of endoplasmic reticulum-derived membranes in the infected cell (8, 9). Bioinformatics, structural biology, (reverse) genetics, and biochemical studies have contributed to the characterization of CoV

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mentioning

confidence: 99%

Molecular Mapping of the RNA Cap 2′-O-Methyltransferase Activation Interface between Severe Acute Respiratory Syndrome Coronavirus nsp10 and nsp16*

Lugari

Betzi

Decroly

et al. 2010

Journal of Biological Chemistry

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“…It has been proved that the severe onset of SARS epidemic in 2003 with over 800 fatalities was evoluted in a market of life-caged dogs market in China. Studies confirmed that caged animals and bats were the potential intermediate hosts [1,2].…”

Section: Introductionmentioning

confidence: 54%

Bioinformatics analysis of the recent MERS-CoV with special reference to the virus-encoded Spike protein

Kandeel¹

2015

Mol Enzyme Drug Targets

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Coronaviruses (CoVs) are characterized by high recombination frequencies, resulting in sudden outbreak of newly evolved viruses with different pathogenicity, tissue tropism and high genome sequence variability. Recently, an outbreak of CoVs was evolved in the Arabian Pennsylvania, which is known as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Full genome sequence analysis of MERS-CoV isolates and its comparison with other CoV full genome sequences revealed a low to medium sequence identity. Furthermore, it showed more sequence identity and phylogenetic relations with batderived CoVs and lower values with animal-derived CoVs, indicating low possibility of zoonotic origin and possible incrimination of bats in the spread of MERS-CoV. The higher neighbor homology was evident with BetaCoV and their associated SARS-CoV. The spike protein, which is a highly variable part of CoV genome and responsible for difference in tissue tropism and virus entry to the cell, showed more or less similar profile of the whole genome analysis. Furthermore, the highest identity was with those in bats with Asian origin of CoV and there was lower homology with isolates from other continents. With low human-to-human transmission and low homology with CoV of animal origin, bats are thought to be the source of MERS-CoV, especially those bearing the Asian isolates of CoV.

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“…Although this was most famously illustrated by the spread of SARS-CoV from Chinese horseshoe bats to human populations during the 2002-2003 epidemic, other coronaviruses such as HCoV-OC43 and bovine coronavirus (BCoV), or feline coronavirus-II, canine coronavirus-II and transmissible gastroenteritis virus(swine virus) are very closely related, consistent with cross-species transmission 19 . This ability to adapt to new environments raised concerns that MERS-CoV would gain virulence and enhanced ability to transmit from human-to-human as the MERS outbreak continued, but this has not occurred.…”

Section: Virology Of Mers-covmentioning

confidence: 95%