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SARS-CoV-2 Spike Affinity and Dynamics Exclude the Strict Requirement of an Intermediate Host
Matteo Castelli; Luigi Scietti; Nicola Clementi; Mattia Cavallaro; Silvia Faravelli; Alberta Pinnola; Elena Criscuolo; Roberta Antonia Diotti; Massimo Clementi; Federico Forneris; Nicasio Mancini.
Affiliation
  • Matteo Castelli; Vita-Salute San Raffaele University
  • Luigi Scietti; University of Pavia - The Armenise-Harvard Laboratory of Structural Biology
  • Nicola Clementi; Vita-Salute San Raffaele University
  • Mattia Cavallaro; Vita-Salute San Raffaele University
  • Silvia Faravelli; University of Pavia - The Armenise-Harvard Laboratory of Structural Biology
  • Alberta Pinnola; University of Pavia - The Armenise-Harvard Laboratory of Structural Biology
  • Elena Criscuolo; Vita-Salute San Raffaele University
  • Roberta Antonia Diotti; Vita-Salute San Raffaele University
  • Massimo Clementi; Vita-Salute San Raffaele University
  • Federico Forneris; Universita degli Studi di Pavia
  • Nicasio Mancini; Vita-Salute San Raffaele University
Preprint in English | bioRxiv | ID: ppbiorxiv-455960
ABSTRACT
SARS-CoV-2 proximal origin is still unclear, limiting the possibility of foreseeing other spillover events with pandemic potential. Here we propose an evolutionary model based on the thorough dissection of SARS-CoV-2 and RaTG13 - the closest bat relative - spike dynamics, kinetics and binding to ACE2. Our results indicate that both spikes share nearly identical, high affinities for Rhinolophus affinis bat and human ACE2, pointing out to negligible species barriers directly related to receptor binding. Also, SARS-CoV-2 spike shows a higher degree of dynamics and kinetics optimization that favors ACE2 engagement. Therefore, we devise an affinity-independent evolutionary process that likely took place in R. affinis bats and limits the eventual involvement of other animal species in initiating the pandemic to the role of vector.
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
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