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Bat and Human Beta2c Coronavirus Comparisions
Recombinomics Commentary 23:15
February 28, 2013

A study which is in press, has shown that a number of different bat species resident in Ghana and parts of Europe are infected with coronaviruses very similar to NCoV, in some cases differing by less than 2% at the genetic level [41]. These findings suggest that NCoV is most likely to have arisen from bat viruses.

A partial RdRp sequence fragment of a P. pipistrellus bat CoV from the Netherlands, termed VM314 (described by us in [10]), was completed toward the 816-bp fragment to refine the RGU classification of EMC/2012. EMC/2012 differed from VM314 by only 1.8%.

The above comments (in red) are from a review of the emergence of the recently describe nCoV, which cites the recent EID publication (in blue) which indicates the human sequence, EMC/2012, differs from the bat sequence from the Netherlands by only 1.8%.  However, this difference is based on the protein sequence of a highly conserved region of a highly conserved gene.  A more sensitive analysis can be obtained by using the actual gene sequence at the nucleotide level, which clearly demonstrates the significant differences between the human coronavirus sequences and those from bats.

The 332BP nucleotide sequence for the Netherlands bat sequence, P.pipi/VM314/2008/NLD, is public, as are the corresponding regions from three bat sequences from the Ukraine (BtCoV/UKR-G17/Pip_nat/UKR/2011) and Romania (BtCoV/8-691/Pip_nat/ROU/2009 and BtCoV/8-724/Pip_pyg/ROU/2009).  Full human sequences have been generated for the fatal case (60M) who died at a hospital in Jeddah, EMC/2012, as well as the sequences from the resident of Qatar (49M) who developed symptoms while practicing Umrah in Saudi Arabia in August, England1, and the index case (60M) for the cluster in the UK who also developed symptoms while practicing Umrah in Saudi Arabia in January, England2.

The differences between the bat sequences from Europe (which are the most closely related public sequences), and the human sequences, are striking.  The three human sequences are identical at all 332 positions, while the bat sequences each have 40-41 differences in the region (representing positions 15311-15612 in the EMC/2012 sequence) or a 88% identity (and the identity is 84% when the human sequences are compared to the bat sequences (HKU-5 series) from Guangdong Province in China. 

This difference between the human and bat sequences is more dramatic in expanded region, which is available for the three sequences from Ukraine and Romania (902 BP representing positions 14771-15672 in the EMC/2012 sequence).  The two sequences generated by the HPA (England1 and England2) are identical at all 902 positions, while the EMC/2012 has two differences (99.8% identity).  In contrast, the most closely related sequence from the European bats is one of the Romanian sequences (BtCoV/8-724/Pip_pyg/ROU/2009), which has 103 differences (88.6% identity), while the closely sequence from Guangdong Province (HKU5-5) has 141 differences (84.4% identity).

The identities cited above demonstrates the conservation of these sequences at the nucleotide level, which provides for a far more sensitive analysis.  In addition to the identities cited above for the conserved region used in the bat study, the full human sequences are approximately 99.5% identical to each other.  Moreover, partial sequences have been generated for the first case (45M) from Riyadh (positions 18105-18414 and 27278-27686) all 719 positions exactly match the sequences from the three human sequences cited above.  Similar levels of identity are seen for the partial sequences from the Qatari case (45M) treated in Germany (the Essen sequences representity positions 15073-15254 and 20598-29838).

Thus, the nucleotide sequences are much more sensitive than the protein sequences for determining the origin of the nCoV isolates from the confirmed cases, and these sequences demonstrate the high level on conservation in the human sequences, which are easily distinguished from bat beta2c coronavirus sequences from Europe, Africa, and Asia.

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