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TitleDistinct pathways for evolution of enhanced receptor binding and cell entry in SARS-like bat coronaviruses.
Journal, issue, pagesPLoS Pathog, Vol. 20, Issue 11, Page e1012704, Year 2024
Publish dateNov 15, 2024
AuthorsAlexandra L Tse / Cory M Acreman / Inna Ricardo-Lax / Jacob Berrigan / Gorka Lasso / Toheeb Balogun / Fiona L Kearns / Lorenzo Casalino / Georgia L McClain / Amartya Mudry Chandran / Charlotte Lemeunier / Rommie E Amaro / Charles M Rice / Rohit K Jangra / Jason S McLellan / Kartik Chandran / Emily Happy Miller /
PubMed AbstractUnderstanding the zoonotic risks posed by bat coronaviruses (CoVs) is critical for pandemic preparedness. Herein, we generated recombinant vesicular stomatitis viruses (rVSVs) bearing spikes from ...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.
External linksPLoS Pathog / PubMed:39546542 / PubMed Central
MethodsEM (single particle)
Resolution3.1 Å
Structure data

45402

9cas

EMDB-45402, PDB-9cas:
Bat SARS-like Coronavirus RsSHC014 Spike Protein
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • bat sars-like coronavirus rsshc014
KeywordsVIRAL PROTEIN / spike / prefusion / coronavirus / bat

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