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. 2023 Jun 27;14(1):3322.
doi: 10.1038/s41467-023-38717-w.

Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

Affiliations

Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

Cedric C S Tan et al. Nat Commun. .

Abstract

There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine complete genomes, including two novel coronavirus species, across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk warrants closer surveillance.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Phylogenetic placement of novel coronaviruses.
a Alignment-free phylogeny of the global diversity of coronavirus genomes (n = 2118) and our nine novel genomes. Host genus (inner ring) and their broader host groups (outer ring) are annotated. Local maximum-likelihood trees of b pedacoviruses (n = 106), c merbecoviruses (n = 113) and d sarbecoviruses (n = 534).
Fig. 2
Fig. 2. RhGB07 can bind and use human ACE2 for cell entry in vitro.
a Entry of different spike pseudoviruses expressing viral glycoproteins into HEK293T cells transfected with (a) human receptors known to allow entry of human coronaviruses or (e) ACE2 homologues from different species. a, e The raw entry values for each pseudoviruses were normalised by their entry into cells transfected with a vector containing no receptor sequence (i.e., “empty”). The raw entry values of representative repeats (n = 3 independent experiments) are also shown for direct comparisons of absolute entry. Representative biolayer interferometry binding curves showing the association and dissociation of SARS-CoV-2 and RhGB07 spike proteins with (b) hACE2 (n = 2 and 3 independent experiments, at three and seven protein concentrations, respectively), or (f) with R. ferrumequinum or M. lucifugus ACE2 (n = 1 independent experiment, at seven protein concentrations). c Entry of pseudoviruses into different “normal” human-cell lines that stably express lower or physiological levels of hACE2. All entry measurements are normalised to those for the “bald” pseudovirus not expressing any spike protein. d Entry of pseudoviruses into Huh7.5 cells transduced with a human TMPRSS2 vector, normalised to “bald”. Data from panels (a, ce) are compiled from n = 3–8 independent experiments and plotted as mean + s.d. Statistical significance was determined by (a, e) two-way ANOVA or c, d one-way ANOVA on log-transformed data (after determining log normality by the Shapiro–Wilk test and QQ plot) with multiple comparisons against “empty” vector or “bald” pseudovirus, respectively. *0.05 ≥ P > 0.01; **0.01 ≥ P > 0.001; ***0.001 ≥ P > 0.0001; ****P ≤ 0.0001. Exact P values annotated for each graph are as follows (from left to right), (a) <0.0001, <0.0001, <0.0001, <0.0001; (c, Calu-3) < 0.0001, <0.0001, 0.001, <0.0001, <0.0001; (c, Caco-2) < 0.0001, <0.0001, 0.022, <0.0001, <0.0001; (c, HEK293T-ACE2) < 0.0001, <0.0001, <0.0001; d <0.0001, <0.0001, <0.0001. (e, SARS-CoV-2) < 0.0001, 0.0003, 0.12, <0.0001, <0.0001 (e, BANAL-20-52) < 0.0001, <0.0001, <0.0001, <0.0001, <0.0001; (e, RatG13) < 0.0001, <0.0001, <0.0001, <0.0001 (e, RhGB07) < 0.0001, <0.0001; (e, RfGB02) < 0.0001.
Fig. 3
Fig. 3. Structural and sequence features of RhGB01-like sarbecoviruses.
a The solved RBD structures of SARS-CoV-2, RaTG13, BANAL-236 (close relative of BANAL-20-52) and the AlphaFold2-predicted structure of RhGB07 were superposed. b The 3D surfaces of the RBD-hACE2 binding interface for SARS-CoV-2 and RhGB07. Alignment of sarbecovirus spike proteins showing the conservation of key contact residues involved interactions between (c) SARS-CoV spike and (d) SARS-CoV-2 spike with hACE2. The sequences shown in the alignments are from Asian, European and African sarbecoviruses that have been shown to bind hACE2. These sequences were ordered based on their genetic relatedness, as inferred from a consensus maximum-likelihood phylogenetic tree reconstructed from their whole genomes (bottom left).

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