Characterization of a MERS-like betacoronavirus in Danish brown long-eared bats (Plecotus auritus) DOI
Camille Melissa Johnston, Vithiagaran Gunalan,

Hans J. Baagøe

et al.

Published: April 29, 2025

Abstract Background Bats are recognized as natural reservoir hosts for numerous viruses and believed to be the evolutionary origin of coronaviruses (CoVs), such SARS-CoV, SARS-CoV-2, possibly MERS-CoV. MERS-like betacoronaviruses have been identified in bat species from Africa, America, Asia, Europe. In this study, we describe first detection characterization a betacoronavirus Danish brown long-eared bats (Plecotus auritus). Methods Fecal samples collected through national surveillance program were screened using pan-CoV RT-qPCRs. Positive underwent ORF1b sequencing, microarray analysis Illumina MiSeq followed by metagenomic assembly full-length genomes. A global phylogenetic tree was used determine placement within Coronaviridae family local maximum likelihood clarified subgroup placement. The receptor-binding potential spike protein human DPP4, ACE2, ACE2 orthologs assessed domain (RBD), alongside homology modeling structural analysis. Results Three tested positive CoVs. One sample Soprano pipistrelle (Pipistrellus pygmaeus) alphacoronavirus sequencing. remaining two samples, obtained colony Plecotus auritus, betacoronaviruses, separate results indicated presence coronavirus. Full genomes successfully assembled approach. Phylogenetic placed them merbecoviruses, forming distinct clade with detected Vespertilionidae Western Europe East Asia. Analysis RBD HKU25 clade. Structural suggested hydrogen bonding patterns between human/bat or similar known in vitro complexes, indicating receptor binding. Conclusion This is report Denmark. analyses reveal that these novel belong clade, preference. Experimental validation needed confirm potential, additional interactions at RBD-receptor interface may differ previously described merbecoviruses. Continued crucial identify intermediate assess interspecies transmission risk, focus on protein, specificity, binding affinity.

Language: Английский

Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor DOI
Jing Chen, Wei Zhang, Yang Li

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

6
Multiple independent acquisitions of ACE2 usage in MERS-related coronaviruses DOI Creative Commons

Chengbao Ma,

Chen Liu, Young‐Jun Park

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

The angiotensin-converting enzyme 2 (ACE2) receptor is shared by various coronaviruses with distinct receptor-binding domain (RBD) architectures, yet our understanding of these convergent acquisition events remains elusive. Here, we report that two bat MERS-related (MERSr-CoVs) infecting Pipistrellus nathusii (P.nat)-MOW15-22 and PnNL2018B-use ACE2 as their receptor, narrow ortholog specificity. Cryoelectron microscopy structures the MOW15-22/PnNL2018B RBD-ACE2 complexes unveil an unexpected entirely binding mode, mapping >45 Å away from any other known ACE2-using coronaviruses. Functional profiling orthologs 105 mammalian species led to identification host tropism determinants, including N432-glycosylation restricting viral recognition, design a soluble P.nat mutant potent neutralizing activity. Our findings reveal usage for merbecoviruses found in European bats, underscoring extraordinary diversity recognition modes among promiscuity this receptor.

Language: Английский

Citations

5
ACE2 utilization of HKU25 clade MERS-related coronaviruses with broad geographic distribution DOI Creative Commons
Chen Liu, Young‐Jun Park,

Chengbao Ma

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract Dipeptidyl peptidase-4 (DPP4) is a well-established receptor for several MERS-related coronaviruses (MERSr-CoVs) isolated from humans, camels, pangolins, and bats (1–6). However, the usage of many genetically diverse bat MERSr-CoVs with broad geographical distributions remains poorly understood. Recent studies have identified angiotensin-converting enzyme 2 (ACE2) as an entry multiple merbecovirus clades. Here, using viral antigen pseudovirus-based functional assays, we demonstrate that merbecoviruses HKU25 clade previously thought to utilize DPP4 (7), employ ACE2 their receptor. Cryo-electron microscopy analysis revealed HsItaly2011 VsCoV-a7 recognize binding mode sharing similarity HKU5 but involving remodeled interfaces distinct ortholog selectivity, suggesting common evolutionary origin utilization these two clades viruses. EjCoV-3, strain closely related DPP4-using MERSr-CoV BtCoV-422, exhibited relatively tropism could human albeit suboptimally. Despite differences in mechanisms spike proteolytic activation compared MERS-CoV, viruses remain sensitive broadly neutralizing antibodies inhibitors. These findings redefine our understanding evolution among highlight versatility coronaviruses. Significance unexpectedly convergently evolved modes across three continents, challenging dogma primary distributed Eurasia host through shared HKU5, prior findings. reveal prevalence show EjCoV-3 preadapted use ACE2, potential spillover. Our data provide blueprint barrier determinants which will facilitate global surveillance development countermeasures against characterized merbecoviruses.

Language: Английский

Citations

0
Global surveillance and countermeasures for ACE2-using MERS-related coronaviruses with spillover risk DOI
Shibo Jiang, Fan Wu

Cell, Journal Year: 2025, Volume and Issue: 188(6), P. 1465 - 1468

Published: March 1, 2025

Language: Английский

Citations

0
Beyond MERS: Merbecovirus receptor plasticity calls for emergence preparedness DOI
Jarel Elgin Tolentino, Spyros Lytras, Jumpei Ito

et al.

Cell Host & Microbe, Journal Year: 2025, Volume and Issue: 33(4), P. 453 - 456

Published: April 1, 2025

Language: Английский

Citations

0
Characterization of a MERS-like betacoronavirus in Danish brown long-eared bats (Plecotus auritus) DOI
Camille Melissa Johnston, Vithiagaran Gunalan,

Hans J. Baagøe

et al.

Published: April 29, 2025

Abstract Background Bats are recognized as natural reservoir hosts for numerous viruses and believed to be the evolutionary origin of coronaviruses (CoVs), such SARS-CoV, SARS-CoV-2, possibly MERS-CoV. MERS-like betacoronaviruses have been identified in bat species from Africa, America, Asia, Europe. In this study, we describe first detection characterization a betacoronavirus Danish brown long-eared bats (Plecotus auritus). Methods Fecal samples collected through national surveillance program were screened using pan-CoV RT-qPCRs. Positive underwent ORF1b sequencing, microarray analysis Illumina MiSeq followed by metagenomic assembly full-length genomes. A global phylogenetic tree was used determine placement within Coronaviridae family local maximum likelihood clarified subgroup placement. The receptor-binding potential spike protein human DPP4, ACE2, ACE2 orthologs assessed domain (RBD), alongside homology modeling structural analysis. Results Three tested positive CoVs. One sample Soprano pipistrelle (Pipistrellus pygmaeus) alphacoronavirus sequencing. remaining two samples, obtained colony Plecotus auritus, betacoronaviruses, separate results indicated presence coronavirus. Full genomes successfully assembled approach. Phylogenetic placed them merbecoviruses, forming distinct clade with detected Vespertilionidae Western Europe East Asia. Analysis RBD HKU25 clade. Structural suggested hydrogen bonding patterns between human/bat or similar known in vitro complexes, indicating receptor binding. Conclusion This is report Denmark. analyses reveal that these novel belong clade, preference. Experimental validation needed confirm potential, additional interactions at RBD-receptor interface may differ previously described merbecoviruses. Continued crucial identify intermediate assess interspecies transmission risk, focus on protein, specificity, binding affinity.

Language: Английский

Citations

0