RaTG13 Is Too Good To Be True.
---- WIV1 pk RaTG13 (2).
Zhiyan-Le, 2021-04-03.
https://sites.google.com/site/zhiyanleback/2021-1/z20210404-wiv1xratg13
https://zhiyanleback.blogspot.com/p/ratg13-is-too-good-to-be-true.html
WHO China trip and its SARS-2 origin report indicated RaTG13 as the SARS-2 origin from nature. Their conclusion was base on: 1]: RaTG13 has 96.2% identity, which was done on the single gene alignment level. 2]: There is only one Amino-Acid difference, which was done on the protein alignment level.
Such conclusion may not stand true. Reason: Alignment and analysis on Codon level are totally ignored, which may lead to different conclusions. Let’s take an example, we have two genomic sequences with the same Am-Acid but different Codons:
Their identities on the Am-Acid or protein level is 100%. And their identities on the single gene alignment level is 56%. See below:
However, their identities on the Codon level: 0%. More over, their structures are different:
Which is accurate? In my view, the one on Codon level is. The reason is simple: When the virus and ACE2 are running, they work on the Codon level. The given samples may have the same Am-Acid, however, their energy level or power can be very different due to their different Codons. This can be well explained by the binary-image Codon Table and by the Buckyball system.
RaTG13 Reality on the Codon Level.
Now using Codon study to see the identities among relevant nCov samples (with GenBank ID):
• NC_045512: WH-01, basic sample, collected from a patient in Wuhan hospital in PRC.
• MN996532: bat RaTG13, said as the most possible origin of SARS-2.
• KF367457: WIV1, the first one of lab-product series of SARS-like nCov.
• NC_028824, Bat-2012, natural bat, collected in PRC Yunnan, 2012.
• NC_030886, Bat-2014. natural bat, collected in PRC Yunnan, 2014
If RaTG13 were a bat from nature in 2013, it should behave as the same or very closely to the two natural bat sample, Bat-2012 and Bat-2014.
Aligning with the basic sample, WH-01 (NC_45512), on the global Codon level, the RaTG13 has a matching score of 184 and WIV1 has 190. And here is the alignment of their Codon base-gene occurring frequency & distribution:
Table 01:
The aligning result: WIV1 has the total gap [-54] and average gap [-14] , and RaTG13 has that of [-206] and [-53]. Both Bat-2012 and Bat-2014 have much bigger gaps.
Clearly, WIV1 is the closest to the basic sample, meaning an obvious greater possibility to be the SARS-2 origin than that of RaTG13, which behaves very differently from natural bat samples.
Ratg13: Too Good To Be True As The SARS-2 Origin.
This indicator, Codon and its genetic frequencies and distribution, is important, according to PRC-PLA doctor Chen Wei (a top virology scientist and Covid-vaccine developer in China; also, she is a leader in charge of medical treatment during the early stage of the pandemic in PRC Wuhan City), because it directly tells the similarity or difference regarding affinity, stability and mutation status/trend, especially genes C & G and their quantity and distribution.
S-Gene is a key factor re SARS-2 interacts with human body. Let’s do some studies on the Codon level by borrowing Dr. Chen Wei suggestion. Below are similarities among the taken samples.
Fig. 01:
Indeed, as Dr. Chen Wei suggested, gene C & G, as well as their quantity and distribution, play an important role, particularly in the Codon 3rd BP genes (where base-gene A & T are 0).
It seems that RaTG13 is in a good position to be the SARS-2 origin: Regarding single gene-aligning closeness to the basic sample NC_045512, WIV1 has a ratio of 0.9866, and RaTG13 has a ratio of 0.9969. However, comparing with natural bats (Bat-2012 and Bat-2014), of which one has the ratio of 0.8892 and another has it of 1.0134, far enough to be role out as the SARS-2 origin by the said sample. That is, sample RaTG13 behaves very differently from natural bats, but it does not.
Further, below is the Codon-leveled aligning result:
Table 02:
The sample RaTG13 has a matching score of 693 occurring aligning similarities, others have it from 87 to 96. The gap between RaTG13 and natural bats is too big to believe that it comes from nature. In a lab field, however, it is pretty easy to reach or even to go beyond 693 similarities score. Besides, RaTG13 similarity ratio is too close to the basic sample but too far from the natural samples. In fact, when using NIH-BLAST to search RaTG13’s all possible similarities, the result has no natural bats but in three categories: synthetic construct, clones, and vaccines, all are lab/man-made work.
In sum, the indicator on Codon level should be in the must-do-list when searching the SARS-2 origin(s). By using it, the picture is very different from what the WHO report said. That is, the sample RaTG13 is too perfect to be a truthful SARS-2 origin from natural bats, rather, it is very likely a lab-product. In contrast, and by all indicators, particularly on the Codon level, WIV1 has the closest relations with basic sample NC_044512, that is, WIV1 is the most possible SARS-2 origin.
Reference:
Message from PLA Vaccine Patent. 2021-03-15.
https://sites.google.com/site/zhiyanleback/2021-1/z20210315-patent-message-en
Data Availability
Table 01-02 (supplement)
Table 02-02 (supplement)