On the molecular mechanism of SARS-CoV-2 retention in the upper respiratory tract

BioRxiv : the Preprint Server for Biology
K. A. ParisCarlos J. Camacho

Abstract

Cell surface receptor engagement is a critical aspect of viral infection. At low pH, binding of SARS-CoV and its ACE2 receptor has a tight interaction that catalyzes the fusion of the spike and endosomal membranes followed by genome release. Largely overlooked has been the role of neutral pH in the respiratory tract, where we find that SARS-CoV stabilizes a transition state that enhances the off-rate from its receptor. An alternative pH-switch is found in CoV-2-like coronaviruses of tropical pangolins, but with a reversed phenotype where the tight interaction with ACE2 is at neutral pH. We show that a single point mutation in pangolin-CoV, unique to CoV-2, that deletes the last His residue in their receptor binding domain perpetuates this tight interaction independent of pH. This tight bond, not present in previous respiratory syndromes, implies that CoV-2 stays bound to the highly expressed ACE2 receptors in the nasal cavity about 100 times longer than CoV. This finding supports the unfamiliar pathology of CoV-2, observed virus retention in upper respiratory tract 1 , longer incubation times and extended periods of shedding. Implications to combat pandemics that, like SARS-CoV-2, export evolutionarily successful strains via hi...Continue Reading

Citations

Jun 7, 2021·Rhinology·M ZugajW J Fokkens

❮ Previous
Next ❯

Datasets Mentioned

BETA
AAU04646
AGZ48806

Software Mentioned

FastContact

Related Concepts

Related Feeds

American Thoracic Society: Allergy, Immunology & Inflammation

This feed has been developed in conjunction with the American Thoracic Society for the benefit of its Allergy, Immunology, and Inflammation Assembly. It highlights new and impactful papers on allergy, asthma, genetics, and the pathogenesis of lung diseases.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

BioRxiv : the Preprint Server for Biology
K. A. ParisCarlos J. Camacho
BioRxiv : the Preprint Server for Biology
Carlos J. CamachoU. Santiago
BioRxiv : the Preprint Server for Biology
Emanuel K Peter, Alexander Schug
© 2021 Meta ULC. All rights reserved