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Evolution of host protease interactions among SARS-CoV-2 variants of concern and related coronaviruses
Edward R Kastenhuber; Marisa Mercadante; Jared L. Johnson; Tomer M. Yaron; Lewis C. Cantley.
Afiliação
  • Edward R Kastenhuber; Weill Cornell Medical College
  • Marisa Mercadante; Weill Cornell Medicine
  • Jared L. Johnson; Weill Cornell Medicine
  • Tomer M. Yaron; Weill Cornell Medicine
  • Lewis C. Cantley; Weill Cornell Medicine
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-496428
ABSTRACT
Previously, we showed that coagulation factors directly cleave SARS-CoV-2 spike and promote viral entry (Kastenhuber et al., 2022). Here, we show that substitutions in the S1/S2 cleavage site observed in SARS-CoV-2 variants of concern (VOCs) exhibit divergent interactions with host proteases, including factor Xa and furin. Nafamostat remains effective to block coagulation factor-mediated cleavage of variant spike sequences. Furthermore, host protease usage has likely been a selection pressure throughout coronavirus evolution, and we observe convergence of distantly related coronaviruses to attain common host protease interactions, including coagulation factors. Interpretation of genomic surveillance of emerging SARS-CoV-2 variants and future zoonotic spillover is supported by functional characterization of recurrent emerging features.
Licença
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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
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