Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

By Xingyi Ge, Jialu Li, Xinglou Yang, Aleksei A. Chmura, Guang-jian Zhu, J. Epstein, J. Mazet, Ben Hu, Wei Zhang, Cheng Peng and 10 more. Nature, 2013

1,656 citations recorded by the source corpus.

The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/417a4b342beca09814e4379b73eda308d7997274

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Citations in the corpus

Correlation between climate indicators and COVID-19 pandemic in New York, USA (2020, background): “Current studies have shown that the transmission route of COVID-19 is bat-human, with intermediate host yet to be identified; it was transmitted mainly by respiratory droplets, as well as human-human transmission (Ge et al., 2013; Huang et al., 2020) .”
Genomic characterization of a novel SARS-CoV-2 (2020, background): “In the future, mining these resources and establishing a statistical framework based on epidemiological, antigenic, and genetic information could provide further insights into the rules that govern the emergence and establishment of antigenically novel variants and improve the potential for SARS-CoV”
Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis (2018, background): “These viruses are poised for emergence because they both efficiently use human ACE2 entry receptors and resist existing vaccines and immunotherapeutics (6, 7).”
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 (2020, neutral): “Detailed investigations indicate that SARS-CoV is transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans (Azhar et al., 2014; Ge et al., 2013; Guan et al., 2003).”
Coronavirus Infections in Children Including COVID-19 (2020, background): “However, SARS-CoV-like viruses can be found in bats, which are known to be able infect human cells without adaptation, making it possible for SARS-CoVs to reemerge 84 (as has now happened with SARS-CoV-2).”
[Asymptomatic infection of COVID-19 and its challenge to epidemic prevention and control]. (2020, background): “In 2013, Ge and colleagues 36 reported the whole genome sequence of a SARS-like coronavirus in bats with that ability to use human ACE2 as a receptor, thus having replication potentials in human cells.”
Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion (2020, neutral): “SARS-CoV is of bat origin and crossed the species barrier using palm civets as putative intermediate hosts (Ge et al., 2013; Li et al., 2005b; Wang et al., 1026 Cell 176, 1026–1039, February 21, 2019 ª 2018 Elsevier Inc. 2005), whereas MERS-CoV is found in dromedary camels as a natural reservoir…”
The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes (2020, background): “of SARSr-CoV, including 2019-nCov, to enter into the cells, indicating the important 23 role of ACE2 in cellular entry [10, 27-29].”