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

Abstract

While the COVID-19 pandemic, caused by SARS-CoV-2, has renewed genomic surveillance efforts in wildlife, there has been limited characterisation of bat-borne coronaviruses in Europe. We collected 48 faecal samples from all but one of the 17 bat species breeding in the UK, through an extensive network of bat rehabilitators and conservationists, and screened them for coronaviruses using deep RNA sequencing. We assembled nine novel, high-quality coronaviral genomes, comprising four alphacoronaviruses from Myotis daubentonii and Pipistrellus pipistrellus, a Middle East respiratory syndrome (MERS)-related coronavirus from Plecotus auritus, and four closely-related sarbecoviruses isolated from both horseshoe bat species Rhinolophus hipposideros and R. ferrumequinum. We further used in vitro assays to demonstrate that at least one of these sarbecoviruses can bind ACE2, the receptor used by SARS-CoV-2 to infect human cells, which was also supported using in silico structural and sequence analyses. Although this sarbecovirus can enter human cells in vitro when ACE2 is over-expressed, our analyses indicate that it is unlikely to infect humans and would require adaptations to do so. Our findings highlight the importance of working collaboratively with conservation networks to enable larger, coordinated viral surveillance efforts and prevent the emergence of zoonoses from wildlife.

Survey of white-footed mice in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses

“…We used a semi-nested pan-coronavirus PCR assay that targets a highly conserved region of the RNA-dependent RNA polymerase (RdRp) gene 43 . A recent study performed a comparison of pan-coronavirus PCR approaches using a set of novel bat coronaviruses and found that our selected approach outperformed 3/4 comparison approaches 44 . Among tested pooled swabs collected in 2022, we noted a 1% (5/468), 0% (0/146), and 0% (0/31) pan-coronavirus PCR positivity among the residential white-footed mice, forested white-footed mice, and deer, respectively.…”

“…We used a semi-nested pan-coronavirus PCR assay that targets a highly conserved region of the RNA-dependent RNA polymerase (RdRp) gene 43 . A recent study performed a comparison of pan-coronavirus PCR approaches using a set of novel bat coronaviruses and found that our selected approach outperformed 3/4 comparison approaches 44 .…”

Detection and characterization of novel luchacoviruses, genusAlphacoronavirus, shed in saliva and feces of meso-carnivores in the northeastern United States

“…For example, genetic comparison of the S1/S2 region between SARS-CoV-2 and closely related CoVs from European bats revealed that a single nucleotide substitution is sufficient to produce a functional furin cleavage site identical to that of SARS-CoV-2 in two bat CoV variants, an essential molecular determinant of their zoonotic potential (21). However, this substitution alone is not enough to enable furin cleavage in similar bat CoVs, possibly because it is in a short loop that may not be accessible to the protease (64). The Luchacovirus clade is closely related to SADS-CoV and bat CoV HKU2 (Figure 1 and 2), which are also characterized for having a recombinant S gene that is more similar to betacoronaviruses than alphacoronaviruses (65).…”

Crossing host boundaries: the evolutionary drivers and correlates of viral host jumps

“…The most likely explanation for this pattern is that some viruses are intrinsically more capable of infecting a diverse range of hosts, possibly by exploiting host-cell machinery that are conserved across different hosts. For example, sarbecoviruses (the subgenus comprising SARS-CoV-2) target the ACE2 host-cell receptor, which is conserved across vertebrates 47,48 , and the high structural conservation of the sarbecovirus spike protein 49 , may explain the observation that single mutations can enable sarbecoviruses to expand their host tropism 50 . In other words, multi-host viruses may have evolved to target more conserved host machinery that reduces the mutational barrier for them to productively infect new hosts.…”

“…Due to resource and logistical constraints, surveillance studies of novel pathogens in animals often have sparse geographical and/or temporal coverage 14,15 , as they focus on selected host and pathogen taxa. Further, many of these studies do not perform downstream characterisation of the novel viruses recovered, and may lack sensitivity due to the use of PCR pre-screening to prioritise samples for sequencing 16 . As such, our understanding of which viruses can, or are likely to emerge, and in which settings is poor.…”