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Saudi Arabia - Middle East respiratory syndrome coronavirus isolate Riyadh_1_2012, complete genome nCoV coronavirus - at Genbank Sept 17, 2013
<table class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;" cellpadding="0" cellspacing="0"><tbody> <tr><td style="text-align: center;"></td></tr> <tr><td class="tr-caption" style="text-align: center;">Click to enlarge. A scale schematic of the first
MERS-CoV genome, EMC/2012.</td></tr> </tbody></table> 45 subgenomic (the smallest is 361 nucleotides [nt])to full length genome (only 13; >30,000nt) fragments of the MERS-CoV have been released onto GenBank ahead of a Lancet Infectious Diseases paper arriving in days. The GenBank accession numbers range form KF600612 - KF600656 but seem to have to be downloaded individually for now. Usually (and hopefully soon), I would get the entire batch using a search of KF600612:KF600656[ACCN] at http://www.ncbi.nlm.nih.gov/nuccore. Most are from cases in Al-Ahsa (adding to the previous 4), as well as from Riyadh, Buraidah and Hafr-Al-Batin Thanks to @Sarah_E_Smith1 for announcing location on GenBank ahead of the Lancet paper.
Posted by Ian M Mackay
<table class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;" cellpadding="0" cellspacing="0"><tbody> <tr><td style="text-align: center;"></td></tr> <tr><td class="tr-caption" style="text-align: center;">Click to enlarge. The primers/probe are depicted as grey boxes.
If mismatches existed they would show up as horizontal black
lines within the grey box. No mismatches are evident.
The GenBank accession numbers are
shown on the left of this alignment of 17 MERS-CoV
sequences.</td></tr> </tbody></table> Only 17 of the 45 sequences seem to include the region covered by the upE laboratory assay I just posted about in the WHO laboratory testing update but of those, the forward and reverse oligonucleotide primers and the probe all bind without any mismatch. While that may sound like an obvious statement considering that these viruses were probably detected using that assay it isn't. The new MERS-CoV sequences were determined using using unbiased 2nd generation high-throughput sequencing technologies that did not rely on these primers to generate them. So we are now able to check and see if there are any nucleotide changes at the target sites for the primers and probe, that would reduce the efficiency the assay. There are no such oligonucleotide mismatches between primer and viral genes among those 17 sequences, which is good news for that assay's continued usefulness. Built to last eh?
Posted by Ian M Mackay
Re: Saudi Arabia - Middle East respiratory syndrome coronavirus isolate Riyadh_1_2012, complete genome nCoV coronavirus - at Genbank Sept 17, 2013
Andrew Rambaut @arambaut 5h
@MackayIM ..... There is no evidence of MERS recomb
in the seqs. CoVs recombine but need coinfection. But given how rare infection is...
Re: Saudi Arabia - Middle East respiratory syndrome coronavirus isolate Riyadh_1_2012, complete genome nCoV coronavirus - at Genbank Sept 17, 2013
Friday, 20 September 2013
Molecular epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV)
And a newcomer to the MERS-CoV birthday celebrations! What great timing to have this released today. The Lancet paper accompanying those recent partial and full genome sequences has been released form its cage. It's a collaborative effort by authors affiliated with the Global Centre for Mass Gatherings Medicine (Ministry of Health Saudi Arabia), Welcome Trust Sanger Institute (United Kingdom) and many other locations. A few highlights of the largest MERS-CoV molecular epidemiology study to date, which includes some great transmission figures and trees (hat tip to the graphics people at Lancet):
Genetic diversity analyses 3 distinct genotypes were identified from human cases in Riyadh
The Al-Ahsa hospital cluster may have had more than 1 viral introduction
Other clusters and standalnone cases can be representd as distinct genoytpes of MERS-CoV, posisbly indicating multiple different virus acquisitions from different sources
Predictive evolutionary analysis suggests an evolutionary rate of 6.3x10<sup>-4</sup> substitutions per nucleotide site per year suggesting a time to the most recent common viral ancestor was July 2011 (ranging from July 2007- June 2012). So we can rule out my harebrained "What If.." MERS-CoV was an endemic virus that we had only just discovered
This evolutionary rate of change suggest more than 1 jump from animal to human was the cause of the outbreak. Unlikely to be just a single introduction followed by human-to-human transmission across Saudi Arabia and beyond. This also reduced any possible R<sub>0</sub> value (the number of cases that 1 case generates, on average, over it's period of infectivity) since transmission events were not a continuous chain but likely to be multiple different spillovers
The rates also suggest it's been substantial period since these viruses shared a common ancestor - so an intermediate host is still a likely culprit for spillover into humans (ongoing studies are examining camels, bats, goats, sheep, dogs, cats, rodents and others - no baboons?)
Contact with goats and camels has been reported in some cases and we know that camels from Oman and Egypt have antibodies to a MERS-CoV-like virus
A particular change in the Spike protein that may impact on its role as a site for enzymatic cleavage (by endosomal furin or trypsin-like proteases) should be further examined (codon 1020; all recent MERS-CoV S protein differ here from the EMC/2012 strain of MERS-CoV exported to the Erasmus Medical Center researchers).
The authors conclude it is imperative that a better understanding of the exposures causing these spillover events must be identified.
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