View source for RaTG13

{{Short description|Close relative of SARS-CoV-2 discovered in 2013}}
{{pp-30-500|small=yes}}
{{Virusbox
| parent = Sarbecovirus 
| species = Severe acute respiratory syndrome–related coronavirus
| strain = BatCoV RaTG13
| synonyms = * Bat coronavirus Ra4991
| synonyms_ref = <ref>{{Cite web|title=Taxonomy browser (Bat coronavirus RaTG13)|url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=2709072|access-date=2021-01-02|website=www.ncbi.nlm.nih.gov}}</ref>
}}

'''Bat coronavirus RaTG13''' is a SARS-like [[betacoronavirus]] identified in the droppings of the horseshoe bat ''[[Intermediate horseshoe bat|Rhinolophus affinis]]''.<ref>{{cite journal | vauthors = Ge XY, Wang N, Zhang W, Hu B, Li B, Zhang YZ, Zhou JH, Luo CM, Yang XL, Wu LJ, Wang B, Zhang Y, Li ZX, Shi ZL | display-authors = 6 | title = Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft | journal = Virologica Sinica | volume = 31 | issue = 1 | pages = 31–40 | date = February 2016 | pmid = 26920708 | pmc = 7090819 | doi = 10.1007/s12250-016-3713-9 }}</ref><ref name="zhou_2020"/> It was discovered in 2013 in bat droppings from a mining cave near the town of Tongguan in [[Mojiang Hani Autonomous County|Mojiang]] county in [[Yunnan]], [[China]].<ref>{{cite journal | vauthors = Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL | display-authors = 6 | title = Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin | journal = Nature | volume = 588 | issue = 7836 | pages = E6 | date = December 2020 | pmid = 33199918 | pmc = 9744119 | doi = 10.1038/s41586-020-2951-z | bibcode = 2020Natur.588E...6Z }}</ref> In February 2020,<ref>{{cite journal | vauthors = Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL | display-authors = 6 | title = A pneumonia outbreak associated with a new coronavirus of probable bat origin | journal = Nature | volume = 579 | issue = 7798 | pages = 270–273 | date = March 2020 | pmid = 32015507 | pmc = 7095418 | doi = 10.1038/s41586-020-2012-7 | bibcode = 2020Natur.579..270Z }}</ref> it was identified as the closest known relative of [[Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]], the virus that causes [[COVID-19]], sharing 96.1% [[Sequence_alignment#Phylogenetic analysis|nucleotide identity]].<ref name="Poudel_2020">{{cite journal | vauthors = Poudel U, Subedi D, Pantha S, Dhakal S | title = Animal coronaviruses and coronavirus disease 2019: Lesson for One Health approach | journal = Open Veterinary Journal | volume = 10 | issue = 3 | pages = 239–251 | date = October 2020 | pmid = 33282694 | pmc = 7703617 | doi = 10.4314/ovj.v10i3.1 | doi-access = free }}</ref><ref name="Hakim" /> However, in 2022, scientists found three closer matches in bats found 530 km south, in [[Feuang district|Feuang]], Laos, designated as [[BANAL-52]] (96.8% identity), [[BANAL-103]] and [[BANAL-236]].<ref>{{cite journal | vauthors = Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, Douangboubpha B, Karami Y, Chrétien D, Sanamxay D, Xayaphet V, Paphaphanh P, Lacoste V, Somlor S, Lakeomany K, Phommavanh N, Pérot P, Dehan O, Amara F, Donati F, Bigot T, Nilges M, Rey FA, van der Werf S, Brey PT, Eloit M | display-authors = 6 | title = Bat coronaviruses related to SARS-CoV-2 and infectious for human cells | journal = Nature | volume = 604 | issue = 7905 | pages = 330–336 | date = April 2022 | pmid = 35172323 | doi = 10.1038/s41586-022-04532-4 | s2cid = 246902858 | doi-access = free | bibcode = 2022Natur.604..330T }}</ref><ref>{{cite journal | vauthors = Mallapaty S | title = Closest known relatives of virus behind COVID-19 found in Laos | journal = Nature | volume = 597 | issue = 7878 | pages = 603 | date = September 2021 | pmid = 34561634 | doi = 10.1038/d41586-021-02596-2 | s2cid = 237626322 | doi-access = free | bibcode = 2021Natur.597..603M }}</ref><ref>{{cite news|title=Newly Discovered Bat Viruses Give Hints to Covid's Origins|date=2021-10-14|url=https://www.nytimes.com/2021/10/14/science/bat-coronaviruses-lab-leak.html|work=New York Times}}</ref>

== History ==
In the spring of 2012, three miners cleaning bat feces in an abandoned copper mine near the town of Tongguan in [[Mojiang Hani Autonomous County]] developed fatal [[pneumonia]].<ref name=NHLV/> Out of concerns that the miner's cases could represent a novel disease,<ref name="Snopes_2021">{{cite web |title=The 'Occam's Razor Argument' Has Not Shifted in Favor of a Lab Leak |url=https://www.snopes.com/news/2021/07/16/lab-leak-evidence/ |website=Snopes.com |date=16 July 2021 |publisher=Snopes |access-date=18 July 2021}}</ref> serum samples collected from the miners were sent to the [[Wuhan Institute of Virology]] and tested by [[Shi Zhengli]] and her group for [[Zaire ebolavirus|Ebola virus]], [[Nipah virus]], and bat SARSr-CoV Rp3. The samples tested negative.<ref name="zhou_2020">{{cite journal | vauthors = Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL | display-authors = 6 | title = Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin | journal = Nature | volume = 588 | issue = 7836 | pages = E6 | date = December 2020 | pmid = 33199918 | pmc = 9744119 | doi = 10.1038/s41586-020-2951-z | doi-access = free | bibcode = 2020Natur.588E...6Z }}</ref><ref name=":1">{{cite journal | vauthors = Ge XY, Wang N, Zhang W, Hu B, Li B, Zhang YZ, Zhou JH, Luo CM, Yang XL, Wu LJ, Wang B, Zhang Y, Li ZX, Shi ZL | display-authors = 6 | title = Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft | journal = Virologica Sinica | volume = 31 | issue = 1 | pages = 31–40 | date = February 2016 | pmid = 26920708 | pmc = 7090819 | doi = 10.1007/s12250-016-3713-9 }}</ref><ref name=NHLV>{{cite journal | vauthors = Wu Z, Yang L, Yang F, Ren X, Jiang J, Dong J, Sun L, Zhu Y, Zhou H, Jin Q | display-authors = 6 | title = Novel Henipa-like virus, Mojiang Paramyxovirus, in rats, China, 2012 | language = en-us | journal = Emerging Infectious Diseases | volume = 20 | issue = 6 | pages = 1064–1066 | date = June 2014 | pmid = 24865545 | pmc = 4036791 | doi = 10.3201/eid2006.131022 | doi-access = free }}</ref>

To uncover a possible cause of the infection, different animals (including bats, rats, and [[Crocidura|musk shrews]]) were also sampled in and around the mining cave. Between 2012 and 2015, Shi Zhengli and her group isolated 293 different [[Coronavirus|coronaviruses]] (284 [[Alphacoronavirus|alpha-]] and 9 [[Betacoronavirus|beta-coronaviruses]]) from bat feces samples in the cave. One of the samples collected in 2013 from ''[[Rhinolophus affinis]]'' (the intermediate horseshoe bat) contained a novel sequence of ribonucleic acids later identified as "RaTG13".<ref name="zhou_2020" /><ref name=":1" /> 

In 2020, Shi and her group retested the serum samples from the miners for SARS-CoV-2. The samples tested negative.<ref name="zhou_2020" />

In 2020, the strain identified in the sample was renamed from the original Ra4991 (4991st sample collected from ''Rhinolophus affinis'') to "RaTG13", to reflect the originating bat species (Ra from ''Rhinolophus affinis''), geographic location (TG from Tongguan), and year collected (13 from 2013).<ref name="snopes:21">{{cite web |title=The 'Occam's Razor Argument' Has Not Shifted in Favor of a COVID Lab Leak |url=https://www.snopes.com/news/2021/07/16/lab-leak-evidence/ |website=Snopes.com |date=16 July 2021 |publisher=Snopes}}</ref> The name change has been considered innuendo by advocates of the [[COVID-19 lab leak theory|lab leak]] theory for the [[COVID-19 pandemic]].<ref name= "snopes:21" />

== Virology ==
The sequence of RaTG13 was reconstructed from [[metagenomic]] sampling (a common practice in environmental virology),<ref name="HarveyHolmes2022">{{cite journal | vauthors = Harvey E, Holmes EC | title = Diversity and evolution of the animal virome | journal = Nature Reviews. Microbiology | volume = 20 | issue = 6 | pages = 321–334 | date = June 2022 | pmid = 34983966 | doi = 10.1038/s41579-021-00665-x | s2cid = 245703661 | doi-access = free }}</ref> and as such, could potentially be an [[chimera (molecular biology)|in-silico chimera]].<ref name="Frutos2022"/> RaTG13 has not been confirmed to exist in nature, to have been cultured or isolated in any laboratory,<ref name="Snopes_2021"/> or to be a viable human pathogen.<ref name="Frutos2022"/> A live virus "RaTG13" has never been detected in any laboratory sample from the WIV or elsewhere.<ref name="Frutos2022">{{cite journal | vauthors = Frutos R, Pliez O, Gavotte L, Devaux CA | title = There is no "origin" to SARS-CoV-2 | journal = Environmental Research | volume = 207 | pages = 112173 | date = May 2022 | pmid = 34626592 | pmc = 8493644 | doi = 10.1016/j.envres.2021.112173 | publisher = Elsevier | bibcode = 2022ER....20712173F }}</ref>

Based on its sequence, RaTG13 is a [[positive-strand RNA virus]] with an outer membrane. Its genome is approximately 29,800 nucleotides. The genome encodes a replicase (ORF1a/1b) and four structural proteins; including a [[coronavirus spike protein|spike protein]] (S), [[coronavirus membrane protein|membrane protein]] (M), [[coronavirus envelope protein|envelope protein]] (E) and [[coronavirus nucleocapsid protein|nucleocapsid protein]] (N); and five [[viral accessory protein]]s, including [[ORF3a]] (NS3), [[ORF6]] (NS6), [[ORF7a]] (NS7a), [[ORF7b]] (NS7b) and [[ORF8]] (NS8).<ref name="zhou_2020" /><ref>{{cite web |url= https://www.ncbi.nlm.nih.gov/nuccore/MN996532 |title=Bat coronavirus RaTG13, complete genome|publisher=[[NCBI]]|access-date=2020-03-28 }}</ref>

RaTG13 bears strong resemblance to the [[SARS-CoV-2]] genome (it shares 96.1% nucleotide similarity), and its identification in animal droppings is a supporting piece of evidence for SARS-CoV-2's natural origin.<ref name=Hakim>{{cite journal | vauthors = Hakim MS | title = SARS-CoV-2, Covid-19, and the debunking of conspiracy theories | journal = Reviews in Medical Virology | volume = 31 | issue = 6 | pages = e2222 | date = November 2021 | pmid = 33586302 | pmc = 7995093 | doi = 10.1002/rmv.2222 | type = Review | doi-access = free }}</ref> The main area of divergence between RaTG13 and SARS-CoV-2 is in the receptor-binding domain (RBD) of the spike protein (S), which is the portion that binds to the receptor protein on the surface of the [[host cell]] and causes infection. The divergence in this domain indicates that, unlike SARS-CoV-2, the RaTG13 virus might not use [[angiotensin-converting enzyme 2]] (ACE2) as its entry site into the cell.<ref name="AndersenRambaut2020">{{cite journal | vauthors = Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF | title = The proximal origin of SARS-CoV-2 | journal = Nature Medicine | volume = 26 | issue = 4 | pages = 450–452 | date = April 2020 | pmid = 32284615 | pmc = 7095063 | doi = 10.1038/s41591-020-0820-9 | doi-access = free }}</ref> Further, the S protein of RaTG13 virus lacks the [[furin]] cleavage motif RRAR↓S.<ref name="AndersenRambaut2020"/>

The binding affinity between RATG13 and hACE2 is lower than that between SARS-CoV-2 RBD and hACE2.<ref>{{cite journal | vauthors = Liu K, Pan X, Li L, Yu F, Zheng A, Du P, Han P, Meng Y, Zhang Y, Wu L, Chen Q, Song C, Jia Y, Niu S, Lu D, Qiao C, Chen Z, Ma D, Ma X, Tan S, Zhao X, Qi J, Gao GF, Wang Q | display-authors = 6 | title = Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species | journal = Cell | volume = 184 | issue = 13 | pages = 3438–3451.e10 | date = June 2021 | pmid = 34139177 | pmc = 8142884 | doi = 10.1016/j.cell.2021.05.031 }}</ref>

==Phylogenetics==
===Phylogenetic tree===

{{SARS-CoV-2 related coronavirus}}
== See also ==
* [[SHC014-CoV|Bat SARS-like coronavirus RsSHC014]]
* [[Bat SARS-like coronavirus WIV1]]
* [[Mòjiāng virus]]

== References ==
{{Reflist}}

{{Coronaviridae}}
{{Taxonbar|from=Q91561236}}

[[Category:SARS-CoV-2]]
[[Category:Bat virome]]
[[Category:Coronaviridae]]
[[Category:Animal virology]]
[[Category:Sarbecovirus]]
[[Category:Zoonoses]]