Bat Coronavirus RaTG13

RaTG13 is a SARS-related coronavirus found in bats and is highly similar to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Specifically, the spike domain is highly similar, however, the receptor-binding site of SARS-CoV-2 diverges genomically and is closer to pangolin SARS-CoVs suggesting a possible recombination event between these viruses in the evolution of SARS-CoV-2.

BatImage Credit: Rudmer Zwerver/

Bat RaTG13

Bat RaTG13 is a SARS-related coronavirus that primarily infects bats. It is a linear 29855bp RNA virus of the betacoronavirus subtype (sarbecovirus). RaTG13 binds to the bat ACE2 receptor through its spike glycoprotein (S-domain).

The bat RaTG13 virus contains a Leu486 in its (S-domain) which accounts for a small buried surface within the viral S-domain and ACE2, allowing it to bind to bat ACE2 (but weaker compared to SARS-CoV-2, discussed below).

Furthermore, there is a tyrosine at the location of Gln493 of SARS-CoV-2 (discussed later), whereas RaTG13 contains a tyrosine residue that does not bind strongly to ACE2 receptor residues. Therefore, RaTG13 does not typically result in infection in bats due to the weaker affinity between its S-domain and bat ACE2 receptor compared to SARS-CoV-2 and human ACE2.  

Links to SARS-CoV-2

SARS-CoV-2 is the virus that causes COVID-19 and is a beta-coronavirus that shares a high degree of sequence homology with horseshoe bat RaTG13 (Yunnan).

The viral S domain shares up to 97.8% conservation in the ectodomain, however, there are many nuclei acid substitutions within the receptor-binding domain; RBD (89.6%). See genomic differences between SARS-CoV-2 and other viruses for more discussion.

As previously mentioned, RaTG13’s S-domain contains a Leu486 whereas human SARS-CoV-2 contains a bulkier Phe486 that binds to a hydrophobic pocket on the surface of ACE2 formed by specific residues e.g. Phe28 & Leu79.

Furthermore, human SARS-CoV-2 contains a Gln493 in the S-domain which makes hydrogen bind with Glu35 of ACE2 that in turn makes a salt bridge link with Lys31 that in itself makes a salt bridge with Gln493, strengthening the binding of SARS-CoV-2 to ACE2.

As discussed, the largest sequence difference is between the bat and the human receptor-binding site (RBD). Compared to the bat RaTG13, the RBD site of SARS-CoV-2 is more closely related to pangolin-SARS-CoV from Guangzhou (MP789/Guandong/2019). It is 97% related, compared to only 77% to bat RaTG13.

The RaTG13 RBD differs to SARS-CoV-2 in that its spike protein does not contain the furin cleavage motif present in SARS-CoV-2.

More conserved features include the RNA-dependent RNA polymerase gene which is highly related between SARS-CoV-2 and RaTG13. However, due to the RBD site being closer to pangolin SARS-CoV, evidence of a recombination event between bat RaTg13 and pangolin SARS-CoV(MP789/Guandong/2019) seems a likely event in SARS-CoV-2 evolution.  

Despite the high degree of similarity in parts related to bat RaTG13 and RBD to pangolin SARS-CoV(MP789/Guandong/2019), the immediate predecessor to human SARS-CoV-2 remains unclear. It is highly likely that pangolin SARS-CoV originated from bat RaTG13 as a result of animal mixing in smuggling centers or animal markets in Wuhan, China.

The ability of SARS-CoV-2 to infect humans and bind with a high affinity to human ACE2 receptors is probably due to the RBD sequence from several bat strains incorporating a pangolin or civet SARS-CoV that has recombinantly evolved due to cross mixing.

Previously, civets in Yunnan, China carrying the bat-borne SARS virus evolved to infect humans in the SARS outbreak of 2002-2003. Thus, it is highly likely a recombination event involving bat RaTG13 amongst other bat SARS-CoVs, pangolin, and/or civet viruses to form SARS-CoV-2.

The origins of SARS-CoV-2


In summary, bat RaTG13 is a betacoronavirus and is highly similar in most parts to human SARS-CoV-2, and as such, is thought to be one of the main contenders as a  direct ancestor to SARS-CoV-2.

However, whilst the overall sequence is related to RaTG13, the RBD site shares a higher homology to pangolin SARS-CoV. This implies that SARS-CoV-2 may have undergone a recombination event due to animal mixing between bats and pangolins in Wuhan, China at some point, before infecting humans.

However, the immediate ancestor to SARS-CoV-2 remains to be identified.

SARS-CoV-2 VirusImage Credit: Kateryna Kon/


  • Lau et al, 2020. Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2. Emerg Infect Dis. 26(7):1542-1547.
  • Li et al, 2020. The divergence between SARS-CoV-2 and RaTG13 might be overestimated due to the extensive RNA modification. Future Virology (ahead of print)
  • Lv et al, 2020. Comparative genomic analysis revealed a specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13. bioRxiv (preprint)
  • Makarenkov et al, 2021. Horizontal gene transfer and recombination analysis of SARS-CoV-2 genes helps discover its close relatives and shed light on its origin. BMC Ecology and Evolution.
  • Malaiyan et al, 2020. An update on the origin of SARS‐CoV‐2: Despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O‐linked glycan residues. Journal of Medical Virology.
  • Matyasek & Kovarik, 2020. Mutation patterns of human SARS-COV-2 and bat RaTG13 coronaviruses genomes are strongly biased towards C>U indicating rapid evolution in their hosts. (preprint)
  • Wrobel et al, 2020. SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Nat Struct Mol Biol.
  • Zhou et al, 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 579:270-273

[further reading: coronavirus disease COVID-19]

Last Updated: Mar 10, 2021

Dr. Osman Shabir

Written by

Dr. Osman Shabir

Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield.


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  1. Rayne Hell Rayne Hell Chile says:

    'Bat RaTG13 is a SARS-related coronavirus that primarily infects bats' seems to contradict 'RaTG13 does not typically result in infection in bats'

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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