On the Oddities and Unusual Characteristics of the 2019-nCoV Virus Genomes and Their Analyses

James Lyons-Weiler, PhD – 2/1/2020

UPDATE – 2/9/2020 – IPAK HAS CONDUCTED FURTHER, IN-DEPTH STUDIES OF THE GENOMIC AN PROTEIN SEQUENCES OF THE 2019-nCoV CORONAVIRUSES AND THEIR RELATIVES AND HAVE COMPELLING RESULTS OF A KEY SIGNATURE USEFUL FOR IDENTIFYING A PARTICULARLY PATHOGENIC CORONAVIRUSES LINEAGE. GIVEN THAT WE HAVE FOUND THIS SIGNATURE, A FUNCTIONAL MOTIF FINGERPRINT, PRESENT IN THE HK-3 CoV FROM 2005, WE BELIEVE THIS EXONERATES RECOMBINATION IN THE LAB AS A SOURCE OF THE VIRUS. THIS DOES NOT EXONERATE ACCIDENTAL RELEASE, HOWEVER. WE ARE WORKING TO PUBLISH OUR FINDINGS.

IN THE INTEREST OF TRANSPARITY, WE ARE KEEPING THE ARTICLE BELOW AS ORIGINALLY PUBLISHED FOR POSTERITY AND PROVENANCE. – JLW

WHEN PHYLOGENETICISTS use sequence data to derive an overall phylogenetic relationship among organisms of viruses, the resulting tree-like pattern is called a phylogenetic tree. In my review of the analysis of the Wuhan coronavirus 2019-nCoV isolated from humans, I emphasized the lack of strong phylogenetic signal from a low “bootstrap” value (100 being highest, <80 usually considered a sign of either insufficient data or something else, like recombination.

That 76 bootstrap value was paired with a de novo appearance of a sequence encoding a SARS-like protein in a virus derived from a bat coronavirus. I had attributed much significance to this finding, as should the rest of the world (i.e., do not reject that the 2019-nCoV is a product of recombination.

There are two ways on this planet for viruses to recombine: in nature, via co-infection with a common host, and in the laboratory. I evaluated the likelihood of those two outcomes two days ago, and the article went viral, helped by the coverage by the Highwire team. Some have misinterpreted the article as saying that I have ruled out a bioweapons origin; however, I have not. The level of evidence supporting an accidental laboratory release of vaccine type, or of a bioweapon, or of a vaccine experiment gone wrong, sensitizing people to serious illnesss and death upon subsequent exposure, are all about the same. What gives a vaccine program the edge is the match between the outcomes in SARS vaccine research in animals and the symptoms and mortality profile of nCoV in humans.

Researchers have been putting SARS protein-encoding genes into viruses since at least 2005. Here’s a study of the use of a SARS-protein gene put into an adenovirus. Here’s another. And they have been putting SARS protein gene sequences into viruses to try to develop vaccines.

Before anyone blame Chinese researchers, one study is from China, another from Korea. German scientists have conducted similar research, and I’m sure the US has, and researchers around the world. Here’s a group of scientists in the US putting the bat coronavirus spike protein into a mouse-adpated SARS.

The placement of 2019-nCoV in a phylogenetic tree nestled within the bat coronaviruses might be assuage some into thinking that there merely been a zoonotic event – transfer of a virus from an animal host to humans – and that therefore the risk of worldwide pandemic from a weaponize or vaccine research or vaccine-escaped coronovirus is low. But it does not.

A new study out of China gives a phylogenetic tree w/out bootstrap values and their result clusters 2019-nCoV within bat coronaviruses, and, oddly, with SARS coronaviruses. This is odd because the prior analyses had placed 2019-nCoV clearly within the bat coronaviruses to the exclusion of SARS coronaviruses. The new Chinese study points to a bat coronavirus as the virus for which we have data that is most similar to 2019-nCoV: HKU9-1.

So let’s look at the neighbors in the tree, HKU9-1, aligned to 2019-nCoV:

See the DOT-plot showing the gaps and the overall gaps shows a disrupted match as well.

It’s all broken up with large gaps of missing sequences. Read how the authors of the paper attribute to multiple rounds of natural recombination “blurring” the relationship:

These scientists are speculating exclusively about natural recombination events, when the sequence they are analyzing has major genomic differences partly inconsistent with the most recent common ancestory of the 2019-nCoV being HKU9-1, in a world in which laboratory recombination research into viruses to make vaccines is 100% known to be ongoing.

We can say with certainty that 2019-nCoV has at least two ancestors: the ancestry of the entire genome, and the ancestry of the SARS spike protein.

I discount the wild recombination idea because natural selection would likely remove individual animals if the recombination occurred in nature due to high mortality. So recombination in the wild is purely speculative.

This looks like an attempt to develop a vaccine to me.

“HIV Sequences” Unsurprising – Maybe

A report of four additional sequences put into the Spike protein, which at the amino acid level are short sequences, but that the nucleotide level are, combined, improbably there by chance, point more toward a bioweapon. The E-values of the match to the HIV sequences are not significant, and there are many more matches to other non-HIV sequences. The presence of all four sequences, the pathogenetic capacity of those additonal novel sequences of are unknown, are of interest to some, but most who understand sequence analysis will attribute their matching to chance.

So who, or what, put SARS spike glycoprotein sequence into 2019-nCoV remains a mystery. Al coronaviruses in all laboratories in China, and around the world for that matter, should be sequenced and in the name of transparency they should all be published so we can all determine the most likely origin. All focus on the origins of the 2019-nCoV virus should include laboratory origin as a leading hypothesis.

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