Posts Tagged ‘Pangolin’

A Very Intriguing Theory about Possible Artificial Origins of COVID-19

April 26, 2020 28 comments

A couple of days ago, I came across a rather long medium post about how COVID-19 aka SARS-2 might have been created in a laboratory rather than through natural selection. While I considered posting a link to it yesterday, it was prudent to do some due diligence first. See.. part of my job and training involves using software tools similar to the ones used in that post, so I decided to first independently verify a few of the main sequence alignments, structural models of proteins and publications etc before promoting it. Well.. while I have not re-verified every single point of data in this post, whatever I have done to date suggests that its main conclusions are correct.

Here is the post: SARS-CoV-2 Genealogy Through the Lens of Gain-of-Function Research

Since this post is very long and technical, let me summarize it- very briefly. The author starts by pointing out the unusual coincidence of an absolutely minimal furin cleavage site evolving at the junction of S1 and S2 subunits of the Spike protein in SARS-2. This is suspicious since gain of function by natural mutations usually tend to first create less than optimal sequences for new functions before being optimized via evolutionary selection. But this virus is too new for such an optimization to have occurred naturally- at least, that is not the most likely explanation.

He then points out that the two viruses which SARS-2 is most similar to ones discovered a few years ago (2014 and 2017/2019) in two different parts of the China. The Bat virus (RaTG13 with 96% similarity) came from a faecal swab from bat droppings from some cave in a part of China that is over 1,000 km from Wuhan, while the Pangolin virus (MP789 – 70% something similarity) came from autopsy of a bunch of smuggled sick pangolins from Malaysia in 2017. He then compares their sequences and while the Bat virus (RaTG13) is very similar to SARS-2, the Pangolin Virus has considerable dissimilarity with SARS-2 in first quarter of sequence for Spike Protein. Homologous recombination in a host infected with two viruses of same “species” without a segmented genome requires them to be very similar to each other.

More curiously, the new furin cleavage site in SARS-2 is a “gain of function” mutation, which means that it allows the virus to be more pathogenic (more infectious or capable of infecting a wider range of hosts/ cell types). It should be noted that more than a couple western research groups tried to insert similar enzymatic cleavage sites into other Coronaviruses such as SARS, MERS etc in the past. So it is not unreasonable to assume that the Chinese group in that Wuhan lab might have also tried it. In fact, we know that multiple research groups in Beijing tried that same gain of function mutation in a chicken Coronavirus. Oh ya.. and they also showed that putting that site into the S protein of another bat Coronavirus allowed it to infect human cells.

He then goes on talk about the whole field of Coronavirus research including many publications by a prominent researcher named Ralph Baric, who pioneered many of these techniques used for creating “gain of function” mutations in Coronaviruses. And yes.. he collaborated with the head of that Wuhan Coronavirus lab over the years, so it is makes perfect sense that you would see some his techniques are used in the later’s lab. Long story short, they looked at many “gain of function” mutations which made the resultant viruses deadlier. Also, Baric’s work seems to be have been “inspirational” to the lab in Wuhan since they kept trying out his ideas on Bat Coronaviruses.

The author then goes on to point out that accidental “leaks” of viruses from secure labs are far more common than most people realize, and are almost always due to poorly or hastily trained staff. So the idea that a poorly trained or careless researcher getting infected, but not developing serious illness and going on to spread it outside the lab is far more plausible than many would like to believe. He also points out the restriction enzyme map of nucleotide sequence, necessary for many types of genetic engineering, is rather similar for SARS-2, Bat and Pangolin coronvirus. And there are some other unusual similarities between the nucleotide codons used for certain amino acids- The explanation for which is a bit technical and complicated.

To summarize, the likelihood that this virus was created (along with others) to study effect of various “gain of function” mutations in Coronaviruses but then accidentally released into community through the actions of a poorly trained junior researcher is much more likely than it evolving naturally from a bat Coronavirus found in some remote part of the Yunnan province in China somehow magically recombining with a Pangolin Coronavirus from Malaysia and gaining just the right fragment of the Spike protein from it.

What do you think? Comments?