RaTG13

Last updated

BatCoV RaTG13
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Pisuviricota
Class: Pisoniviricetes
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Sarbecovirus
Species:
Severe acute respiratory syndrome–related coronavirus
Strain:
BatCoV RaTG13
Synonyms [1]
  • Bat coronavirus Ra4991

Bat coronavirus RaTG13 is a SARS-like betacoronavirus identified in the droppings of the horseshoe bat Rhinolophus affinis . [2] [3] It was discovered in 2013 in bat droppings from a mining cave near the town of Tongguan in Mojiang county in Yunnan, China. [4] In February 2020, [5] it was identified as the closest known relative of SARS-CoV-2, the virus that causes COVID-19, sharing 96.1% nucleotide identity. [6] [7] However, in 2022, scientists found three closer matches in bats found 530 km south, in Feuang, Laos, designated as BANAL-52 (96.8% identity), BANAL-103 and BANAL-236. [8] [9] [10]

Contents

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. [11] Out of concerns that the miner's cases could represent a novel disease, [12] serum samples collected from the miners were sent to the Wuhan Institute of Virology and tested by Shi Zhengli and her group for Ebola virus, Nipah virus, and bat SARSr-CoV Rp3. The samples tested negative. [3] [13] [11]

To uncover a possible cause of the infection, different animals (including bats, rats, and musk shrews) were also sampled in and around the mining cave. Between 2012 and 2015, Shi Zhengli and her group isolated 293 different coronaviruses (284 alpha- and 9 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". [3] [13]

In 2020, Shi and her group retested the serum samples from the miners for SARS-CoV-2. The samples tested negative. [3]

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). [14] The name change has been considered innuendo by advocates of the lab leak theory for the COVID-19 pandemic. [14]

Virology

The sequence of RaTG13 was reconstructed from metagenomic sampling (a common practice in environmental virology), [15] and as such, could potentially be an in-silico chimera. [16] RaTG13 has not been confirmed to exist in nature, to have been cultured or isolated in any laboratory, [12] or to be a viable human pathogen. [16] A live virus "RaTG13" has never been detected in any laboratory sample from the WIV or elsewhere. [16]

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 spike protein (S), membrane protein (M), envelope protein (E) and nucleocapsid protein (N); and five viral accessory proteins, including ORF3a (NS3), ORF6 (NS6), ORF7a (NS7a), ORF7b (NS7b) and ORF8 (NS8). [3] [17]

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. [7] 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. [18] Further, the S protein of RaTG13 virus lacks the furin cleavage motif RRAR↓S. [18]

The binding affinity between RATG13 and hACE2 is lower than that between SARS-CoV-2 RBD and hACE2. [19]

Phylogenetics

Phylogenetic tree

A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is: [20] [21]

SARS‑CoV‑2 related coronavirus

(Bat) Rc-o319, 81% to SARS-CoV-2, Rhinolophus cornutus , Iwate, Japan [22]

Bat SL-ZXC21, 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan, Zhejiang [23]

Bat SL-ZC45, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang [23]

Pangolin SARSr-CoV-GX, 85.3% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia [24]

Pangolin SARSr-CoV-GD, 90.1% to SARS-CoV-2, Manis javanica, smuggled from Southeast Asia [25]

Bat RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng, Cambodia [26]

Bat RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli, Steung Treng, Cambodia [26]

(Bat) RacCS203, 91.5% to SARS-CoV-2, Rhinolophus acuminatus , Chachoengsao, Thailand [21]

(Bat) RmYN02, 93.3% to SARS-CoV-2, Rhinolophus malayanus , Mengla, Yunnan [27]

(Bat) RpYN06, 94.4% to SARS-CoV-2, Rhinolophus pusillus, Xishuangbanna, Yunnan [20]

(Bat) RaTG13, 96.1% to SARS-CoV-2, Rhinolophus affinis , Mojiang, Yunnan [28]

(Bat) BANAL-52, 96.8% to SARS-CoV-2, Rhinolophus malayanus , Vientiane, Laos [29]

SARS-CoV-2

SARS-CoV-1, 79% to SARS-CoV-2

See also

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Betacoronavirus pandemicum is a species of virus consisting of many known strains. Two strains of the virus have caused outbreaks of severe respiratory diseases in humans: severe acute respiratory syndrome coronavirus 1, the cause of the 2002–2004 outbreak of severe acute respiratory syndrome (SARS), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the pandemic of COVID-19. There are hundreds of other strains of SARSr-CoV, which are only known to infect non-human mammal species: bats are a major reservoir of many strains of SARSr-CoV; several strains have been identified in Himalayan palm civets, which were likely ancestors of SARS-CoV-1.

<span class="mw-page-title-main">SARS-CoV-1</span> Virus that causes SARS

Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), previously known as severe acute respiratory syndrome coronavirus (SARS-CoV), is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for the 2002–2004 SARS outbreak. It is an enveloped, positive-sense, single-stranded RNA virus that infects the epithelial cells within the lungs. The virus enters the host cell by binding to angiotensin-converting enzyme 2. It infects humans, bats, and palm civets. The SARS-CoV-1 outbreak was largely brought under control by simple public health measures. Testing people with symptoms, isolating and quarantining suspected cases, and restricting travel all had an effect. SARS-CoV-1 was most transmissible when patients were sick, so its spread could be effectively suppressed by isolating patients with symptoms.

Novel coronavirus (nCoV) is a provisional name given to coronaviruses of medical significance before a permanent name is decided upon. Although coronaviruses are endemic in humans and infections normally mild, such as the common cold, cross-species transmission has produced some unusually virulent strains which can cause viral pneumonia and in serious cases even acute respiratory distress syndrome and death.

<i>Betacoronavirus</i> Genus of viruses

Betacoronavirus is one of four genera of coronaviruses. Member viruses are enveloped, positive-strand RNA viruses that infect mammals, including humans. The natural reservoir for betacoronaviruses are bats and rodents. Rodents are the reservoir for the subgenus Embecovirus, while bats are the reservoir for the other subgenera.

Bat SARS-like coronavirus WIV1, also sometimes called SARS-like coronavirus WIV1, is a strain of severe acute respiratory syndrome–related coronavirus (SARSr-CoV) isolated from Chinese rufous horseshoe bats in 2013. Like all coronaviruses, virions consist of single-stranded positive-sense RNA enclosed within an envelope.

Shi Zhengli is a Chinese virologist who researches SARS-like coronaviruses of bat origin. Shi directs the Center for Emerging Infectious Diseases at the Wuhan Institute of Virology (WIV). In 2017, Shi and her colleague Cui Jie discovered that the SARS coronavirus likely originated in a population of cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan. She came to prominence in the popular press as "Batwoman" during the COVID-19 pandemic for her work with bat coronaviruses. Shi was included in Time's 100 Most Influential People of 2020.

<span class="mw-page-title-main">SARS-CoV-2</span> Virus that causes COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the provisional name 2019 novel coronavirus (2019-nCoV), and has also been called human coronavirus 2019. First identified in the city of Wuhan, Hubei, China, the World Health Organization designated the outbreak a public health emergency of international concern from January 30, 2020, to May 5, 2023. SARS‑CoV‑2 is a positive-sense single-stranded RNA virus that is contagious in humans.

<span class="mw-page-title-main">Wuhan Institute of Virology</span> Research Institute in Wuhan, Hubei, China

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<span class="mw-page-title-main">Mòjiāng virus</span> Species of virus

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<span class="mw-page-title-main">ORF8</span> Gene that encodes a viral accessory protein

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LYRa11 is a SARS-like coronavirus (SL-COV) which was identified in 2011 in samples of intermediate horseshoe bats in Baoshan, Yunnan, China. The genome of this virus strain is 29805nt long, and the similarity to the whole genome sequence of SARS-CoV that caused the SARS outbreak is 91%. It was published in 2014. Like SARS-CoV and SARS-CoV-2, LYRa11 virus uses ACE2 as a receptor for infecting cells.

ZC45 and ZXC21, sometimes known as the Zhoushan virus, are two bat-derived strains of severe acute respiratory syndrome–related coronavirus. They were collected from least horseshoe bats by personnel from military laboratories in the Third Military Medical University and the Research Institute for Medicine of Nanjing Command between July 2015 and February 2017 from sites in Zhoushan, Zhejiang, China, and published in 2018. These two virus strains belong to the clade of SARS-CoV-2, the virus strain that causes COVID-19, sharing 88% nucleotide identity at the scale of the complete virus genome.

<span class="mw-page-title-main">Zoonotic origins of COVID-19</span> Theories on how COVID-19 originated in animals

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References

  1. ↑ "Taxonomy browser (Bat coronavirus RaTG13)". www.ncbi.nlm.nih.gov. Retrieved 2021-01-02.
  2. ↑ Ge XY, Wang N, Zhang W, Hu B, Li B, Zhang YZ, et al. (February 2016). "Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft". Virologica Sinica. 31 (1): 31–40. doi:10.1007/s12250-016-3713-9. PMC   7090819 . PMID   26920708.
  3. 1 2 3 4 5 Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (December 2020). "Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 588 (7836): E6. Bibcode:2020Natur.588E...6Z. doi: 10.1038/s41586-020-2951-z . PMC   9744119 . PMID   33199918.
  4. ↑ Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (December 2020). "Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 588 (7836): E6. Bibcode:2020Natur.588E...6Z. doi:10.1038/s41586-020-2951-z. PMC   9744119 . PMID   33199918.
  5. ↑ Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (March 2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. Bibcode:2020Natur.579..270Z. doi:10.1038/s41586-020-2012-7. PMC   7095418 . PMID   32015507.
  6. ↑ Poudel U, Subedi D, Pantha S, Dhakal S (October 2020). "Animal coronaviruses and coronavirus disease 2019: Lesson for One Health approach". Open Veterinary Journal. 10 (3): 239–251. doi: 10.4314/ovj.v10i3.1 . PMC   7703617 . PMID   33282694.
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  8. ↑ Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, et al. (April 2022). "Bat coronaviruses related to SARS-CoV-2 and infectious for human cells". Nature. 604 (7905): 330–336. Bibcode:2022Natur.604..330T. doi: 10.1038/s41586-022-04532-4 . PMID   35172323. S2CID   246902858.
  9. ↑ Mallapaty S (September 2021). "Closest known relatives of virus behind COVID-19 found in Laos". Nature. 597 (7878): 603. Bibcode:2021Natur.597..603M. doi: 10.1038/d41586-021-02596-2 . PMID   34561634. S2CID   237626322.
  10. ↑ "Newly Discovered Bat Viruses Give Hints to Covid's Origins". New York Times. 2021-10-14.
  11. 1 2 Wu Z, Yang L, Yang F, Ren X, Jiang J, Dong J, et al. (June 2014). "Novel Henipa-like virus, Mojiang Paramyxovirus, in rats, China, 2012". Emerging Infectious Diseases. 20 (6): 1064–1066. doi: 10.3201/eid2006.131022 . PMC   4036791 . PMID   24865545.
  12. 1 2 "The 'Occam's Razor Argument' Has Not Shifted in Favor of a Lab Leak". Snopes.com. Snopes. 16 July 2021. Retrieved 18 July 2021.
  13. 1 2 Ge XY, Wang N, Zhang W, Hu B, Li B, Zhang YZ, et al. (February 2016). "Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft". Virologica Sinica. 31 (1): 31–40. doi:10.1007/s12250-016-3713-9. PMC   7090819 . PMID   26920708.
  14. 1 2 "The 'Occam's Razor Argument' Has Not Shifted in Favor of a COVID Lab Leak". Snopes.com. Snopes. 16 July 2021.
  15. ↑ Harvey E, Holmes EC (June 2022). "Diversity and evolution of the animal virome". Nature Reviews. Microbiology. 20 (6): 321–334. doi: 10.1038/s41579-021-00665-x . PMID   34983966. S2CID   245703661.
  16. 1 2 3 Frutos R, Pliez O, Gavotte L, Devaux CA (May 2022). "There is no "origin" to SARS-CoV-2". Environmental Research. 207. Elsevier: 112173. Bibcode:2022ER....20712173F. doi:10.1016/j.envres.2021.112173. PMC   8493644 . PMID   34626592.
  17. ↑ "Bat coronavirus RaTG13, complete genome". NCBI . Retrieved 2020-03-28.
  18. 1 2 Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF (April 2020). "The proximal origin of SARS-CoV-2". Nature Medicine. 26 (4): 450–452. doi: 10.1038/s41591-020-0820-9 . PMC   7095063 . PMID   32284615.
  19. ↑ Liu K, Pan X, Li L, Yu F, Zheng A, Du P, et al. (June 2021). "Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species". Cell. 184 (13): 3438–3451.e10. doi:10.1016/j.cell.2021.05.031. PMC   8142884 . PMID   34139177.
  20. 1 2 Zhou H, Ji J, Chen X, Bi Y, Li J, Wang Q, et al. (August 2021). "Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses". Cell. 184 (17): 4380–4391.e14. doi:10.1016/j.cell.2021.06.008. PMC   8188299 . PMID   34147139.
  21. 1 2 Wacharapluesadee S, Tan CW, Maneeorn P, Duengkae P, Zhu F, Joyjinda Y, et al. (February 2021). "Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia". Nature Communications. 12 (1): 972. Bibcode:2021NatCo..12..972W. doi: 10.1038/s41467-021-21240-1 . PMC   7873279 . PMID   33563978.
  22. ↑ Murakami S, Kitamura T, Suzuki J, Sato R, Aoi T, Fujii M, et al. (December 2020). "Detection and Characterization of Bat Sarbecovirus Phylogenetically Related to SARS-CoV-2, Japan". Emerging Infectious Diseases. 26 (12): 3025–3029. doi:10.3201/eid2612.203386. PMC   7706965 . PMID   33219796.
  23. 1 2 Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, et al. (June 2020). "A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein". Current Biology. 30 (11): 2196–2203.e3. doi:10.1016/j.cub.2020.05.023. PMC   7211627 . PMID   32416074.
  24. ↑ Lam TT, Jia N, Zhang YW, Shum MH, Jiang JF, Zhu HC, et al. (July 2020). "Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins". Nature. 583 (7815): 282–285. Bibcode:2020Natur.583..282L. doi:10.1038/s41586-020-2169-0. PMID   32218527. S2CID   214683303.
  25. ↑ Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou JJ, et al. (July 2020). "Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins". Nature. 583 (7815): 286–289. Bibcode:2020Natur.583..286X. doi:10.1038/s41586-020-2313-x. PMID   32380510. S2CID   256822274.
  26. 1 2 Delaune D, Hul V, Karlsson EA, Hassanin A, Ou TP, Baidaliuk A, et al. (November 2021). "A novel SARS-CoV-2 related coronavirus in bats from Cambodia". Nature Communications. 12 (1): 6563. Bibcode:2021NatCo..12.6563D. doi:10.1038/s41467-021-26809-4. PMC   8578604 . PMID   34753934.
  27. ↑ Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, et al. (June 2020). "A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein". Current Biology. 30 (11): 2196–2203.e3. doi:10.1016/j.cub.2020.05.023. PMC   7211627 . PMID   32416074.
  28. ↑ Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. (March 2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. Bibcode:2020Natur.579..270Z. doi:10.1038/s41586-020-2012-7. PMC   7095418 . PMID   32015507.
  29. ↑ Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, et al. (April 2022). "Bat coronaviruses related to SARS-CoV-2 and infectious for human cells". Nature. 604 (7905): 330–336. Bibcode:2022Natur.604..330T. doi:10.1038/s41586-022-04532-4. PMID   35172323. S2CID   246902858.
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