Distinct pathways for evolution of enhanced receptor binding and cell entry in SARS-like bat coronaviruses.

Publication date: Nov 15, 2024

Understanding the zoonotic risks posed by bat coronaviruses (CoVs) is critical for pandemic preparedness. Herein, we generated recombinant vesicular stomatitis viruses (rVSVs) bearing spikes from divergent bat CoVs to investigate their cell entry mechanisms. Unexpectedly, the successful recovery of rVSVs bearing the spike from SHC014-CoV, a SARS-like bat CoV, was associated with the acquisition of a novel substitution in the S2 fusion peptide-proximal region (FPPR). This substitution enhanced viral entry in both VSV and coronavirus contexts by increasing the availability of the spike receptor-binding domain to recognize its cellular receptor, ACE2. A second substitution in the S1 N-terminal domain, uncovered through the rescue and serial passage of a virus bearing the FPPR substitution, further enhanced spike:ACE2 interaction and viral entry. Our findings identify genetic pathways for adaptation by bat CoVs during spillover and host-to-host transmission, fitness trade-offs inherent to these pathways, and potential Achilles’ heels that could be targeted with countermeasures.

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Concepts Keywords
Bat Bat
Coronaviruses Bearing
Fitness Binding
Genetic Coronaviruses
Zoonotic Cov
Covs
Enhanced
Entry
Fppr
Pathways
Receptor
Rvsvs
Sars
Spike
Substitution

Semantics

Type Source Name
disease IDO cell
disease MESH vesicular stomatitis
disease IDO host
disease MESH Infectious Disease
pathway REACTOME Infectious disease
disease IDO history
disease IDO process
pathway REACTOME Reproduction
disease MESH infection
disease IDO assay
drug DRUGBANK Coenzyme M
disease IDO virulence
disease MESH point mutation
disease IDO replication
drug DRUGBANK Amino acids
disease IDO protein
drug DRUGBANK Alpha-Linolenic Acid
disease IDO infectivity
disease MESH astrocytoma

Original Article

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