Understanding the Origin of ‘BatCoVRaTG13’, a Virus Closest to SARS-CoV-2

[Emily]

https://www.preprints.org/manuscript/202005.0322/v2

Working Paper Short Note Version 2 This version is not peer-reviewed

Rahalkar, M.C.; Bahulikar, R.A. Understanding the Origin of ‘BatCoVRaTG13’, a Virus Closest to SARS-CoV-2. Preprints 2020, 2020050322
Abstract

Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% ¹. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp ². BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang ². Both the publications ^1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China ³. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 ¹ where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ^3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.
Subject Areas


SARS-CoV-2; RATG13; BtCoV/4991; SARS-like (SL-) corona virus; pneumonia


Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)


Comment 1
Received: 24 May 2020
Commenter: Monali Rahalkar
Commenter's Conflict of Interests: Author
Comment: Added to the abstract (Page 2)These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ^3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted. Page 4 and page 5 added content:has been also predicted in a preprint ⁶ and mentioned on a Chinese Database of bat-associated viruses (http://www.mgc.ac.cn/cgi-bin/DBatVir...n&acc=MN996532). Severe pneumonia cases and deaths in miners working in a mineshaft,Mojiang, Yunnan, ChinaIn April-May 2012, six mineworkers were involved in removing debris from a mineshaft filled with bats and bat faeces, in the Mojiang region, Yunnan, China ⁴. It was noted that after exposure to the bat faeces for a varying period of time these miners started experiencing fever and signs of severe pneumonia and were admitted to the emergency department affiliated to Kunming Medical University. A master’s thesis entitled ‘The analysis of 6 patients with severe pneumonia caused by unknown viruses’ described the details of diagnosis, treatment and probable causes of the infections and deaths ⁴. Three of the mineworkers succumbed to the infection and died while three of them survived ⁴. The cause of the pneumonia was diagnosed to be primarily of a viral origin (related to bats) and secondary infections due to fungus or bacteria were also seen by experts ⁴. The inferences drawn in the thesis based on the six miners were that the shorter time the workers spent in the mine (clearing the bat faeces) and younger the age, the prognosis of these patients was better and the hospital stay was shorter. The treatment included the use of antiviral, antibacterial, antifungal antibiotics, along with cortico-steroids and antithrombotic drugs (in a few patients). Page 7 added: Six mine workers who cleared the debris (mainly bat faeces) from the same mineshafts suffered from atypical pneumonia and three of them died. This reference also has not been mentioned in Zhou et al 2020 ¹. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted. Although the genomic composition of SARS-CoV-2 and RaTG13 differ by 4%, it was important to report and refer to the exact sample and conditions from which RaTG13 sequence was derived ¹. All these facts should be considered in light of the present Covid-19, by scientists, doctors and academicians.

[bertrand789]

thank you,

I like this story well. Accidents in mines: it is normal in this environment, to make fun of employees, much more, than in agriculture. In such cases, only the doctors are there. Without at least two deaths, we do not think, and we see the results ... We can criticize the agricultural sectors, but whatever, if it affects food, you have to be serious. You have to be serious, because the file will be processed. There these actors are all on deck and their vigilance will not be relaxed ...

In the mining sector, with a little money, there is always a solution ...
Do not say where it is, an open secret, which indicates, only that this file must have current dimensions ... In any case, I doubt that in China, as elsewhere, we can take samples from mines, without the owners' agreement. That these owners use the services of a professor of philosophy, and of doctors, without any real means, this is consistent ... This greatly clarifies the management problems mentioned *:

- monitoring of human personnel in mines,
- ecological impact studies of mining activities
they are real subjects

You found the danger card and the rules to implement for these two subjects, there and elsewhere, because there are staff who work under the ground with bats, example metros, all trades of the water ...

Monitoring black waters, this must have started to make them think, a little ... By pointing, a little better, as if by magic, they will certainly regain their memory. This is a file where India has always shone: respect for water ...


* see old post, on the purpose of certain structures ...

[Emily]

5-FU is being explored for anti-viral activity against SARS-CoV-2. I would think that would have been attempted with BtCoV/4991 (aka RaTG13) at one of the labs in Wuhan. The stated purpose for collecting samples of wild bat viruses was to develop therapeutics prior to a pandemic. If RaTG13's proofreading ability failed, then maybe that is how SARS-CoV-2 emerged. I doubt the work was done under more than BSL-2 precautions since RaTG13 wasn't thought to be terribly virulent, (host age and health and co-existent pathogens in the cave were thought to be a big part in the miner deaths.) The morbidity/mortality of SARS-CoV-2 is very similar to BtCoV/4991-RaTG13. It's the transmissibility that has changed.

https://www.biorxiv.org/content/10.1....969006v1.full

Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13

Longxian Lv, Gaolei Li, Jinhui Chen, Xinle Liang, Yudong Li
bioRxiv 2020.02.27.969006; doi: https://doi.org/10.1101/2020.02.27.969006 This article is a preprint and has not been certified by peer review [what does this mean?].

Conclusions

Through comprehensive comparative analysis between SARS-CoV-2 and other coronaviruses, we found the synonymous mutations is dramatically elevated between SARS-CoV-2 and RaTG13 than that of other coronavirus strains, and the nucleotide mutations were enriched in T:C transition. The specific mutation pattern may caused by the loss function of RNA 3’-to-5’ exoribonuclease (ExoN). Moreover, as the SARS-CoV-2 was supposed to be originated from Bat-SARSr-CoV RaTG13, the increased synonymous substitution between SARS-CoV-2 and RaTG13 strain suggested the SARS-CoV-2 genome was under stronger negative (purifying) selection. We also detected some sites in spike protein was experiencing positive selection. These observations suggest that adaptive evolution might contribute to its host shifts. However, as the RNA mutagen (e.g. 5-FU) could induce the same mutation pattern, the mechanism of the mutation pattern observed between SARS-CoV-2 and RaTG13 should be further investigated in future work.